Harold H. Zakon - US grants

neurotransmitter receptor; neurophysiology; steroid hormone; protein biosynthesis; hormone regulation /control mechanism; voltage /patch clamp;

Scientists have long been interested in understanding the neural processes underlying perception. In humans, these processes and the sensory stimuli themselves are often so complicated that a complete understanding of the perceptual process is elusive. Much progress has been made, however, with simpler animal models in which (1) the sensory stimulus in question is easily quantifiable and can be manipulated, (2) there is a way to tell if the animal can detect the stimulus, and (3) the response properties of the neurons responsible for the perception can be measured directly. Electric fish provide such a model system. Dr. Zakon's research involves a species of fish that continuously produces a weak electric field from an organ in its tail. This field (the electric organ discharge, or EOD) surrounds the fish's body. The animal is able to navigate and localize objects in dark, murky water by detecting distortions in the electric field with specialized electroreceptors on the body surface. The EOD is also used extensively in communication between fish. The EOD voltage varies in a nearly sinusoidal fashion. The EOD frequency of each individual is unique, and that of males and females differs by roughly an octave. The electroreceptors are tuned to the fish's own EOD frequency and are much less sensitive to other frequencies. How, then, does the fish perceive the EODs produced by members of the opposite sex? When two electric fish are close to each other, each fish's electroreceptors are stimulated by a signal that is the sum of the two EODs. This interaction of EOD signals probably allows the fish to detect each other's EODs. Using behavioral training and neurophysiological recording techniques, Dr. Zakon is studying how these summed EOD signals are perceived and how information about the presence of another fish is extracted from this signal. Dr. Zakon's research is elucidating the perception and analysis of a biologically relevant stimulus. This understanding can be gained because electric fish often rely on electrical signals for the detection of other members of the species and because electrical signals are easy to measure and manipulate. The underlying processes of signal analysis elucidated should be useful in understanding perceptual systems in other vertebrates.

This proposal aims to understand the cellular mechanisms by which sex stero d hormones (androgens, estrogens) alter the waveshape of spikes generated by the electric organ in a species of fish with a sexually dimorphic electric organ discharge. The 7 sections described herein can be summarized as an attempt to describe the action of steroid hormones on the biophysical properties, specifically ion conductances, of this tissue. In addition, these cells will be analyzed morphologically to determine the extent of synaptic and spiking membrane as this will aid in the interpretation of the biophysical data. Also, a medullary nucleus, called the pacemaker nucleus, which drives the electric organ, will be investigated in terms of its potential role in influencing spike waveshape in the electric organ. The significance of this study is two fold. First, by understanding how steroid hormones alter the ion conductances of excitable cells, this work will fill in the "black-box" between sex steroids and behavior. It is know where sex steroids bind in the brain and that they may alter neural activit , but their mechanisms re unknown. Thus, this may be a benefit to an understanding of hormonal modulation of behavior and, perhaps, sexual dysfunction. The other, more general, point is that this work will illuminate the fundamental question of how excitability of an excitable membrane may be regulated.

The tuberous electroreceptors of weakly electric fish are related to hair cells of the lateral line and inner ear. Like some hair cells, they are tuned by an electrical filter in their basal membranes. The number of sensory cells in each organ increases throughout the fish's life, the new sensory cells being produced by support cells. Furthermore, after skin has been removed new skin regrows in the wound and tuberous receptor organs regenerate, we believe, from the support cells of intact organs in the surrounding skin that migrate into the regenerating skin. During regeneration the tuberous organ begins as a layer of support cells around a lumen, and these support cells also give rise to the new sensory cells. These receptors show a dependence on their innervation in that receptor organs become disrupted and lose sensory receptor cells 2-3 weeks after denervation. Receptor organs also do not appear in denervated skin. We wish to answer the following questions in this proposal. 1) Does receptor cell tuning change after denervation? 2) What morphological changes occur in receptors as they degenerate and what changes, if any, occur in the support cells? 3) What role does innervation play in stimulating support cells to become mitotic and add new sensory cells in intact organs? 4) What role does innervation play in the early regeneration of tuberous sensory organs and, do organs regenerate if the new skin is surrounded by old organs that are denervated? 5) Are newly regenerated organs especially sensitive to denervation? 6) How do rates of mitosis change in support cells of regenerating organs after denervation? The results from this study will increase our fundamental understanding of the process of sensory cell regeneration and the putative trophic influence of afferent nerves upon their sensory cells.

Funds are provided to defray travel costs of young scientists and invited participants to attend the Conference on Steroid Action on Excitable Cells which is to be held as a Satellite Symposium at the 1993 Society for Neuroscience on November 6, 1993 in Washington, DC. Since the 1960's, it has been readily accepted that the mechanism of steroid hormone action is by a genomic route. However, in some circumstances, hormones can have effects within seconds to minutes. Until recently, these data were ignored because it did not fit the dogma. Now it has become clear that steroid action in the brain is more complex than that previously thought. Indeed, steroid action is mediated by both genomic and non-genomic routes. The conference will address the mechanisms through which steroid hormones and thyroid hormones act on excitable cells. The presentations will highlight the exciting recent work on (1) the modulatory action of steroid on amino acid receptors in the hippocampus; (2) the use of simple model systems as means to examine the actions of hormones on identified, voltage-clamped, ion currents; (3) novel hormone receptors; and (4) the molecular and biochemical actions of steroids. These are fundamentally important questions in an field that is rapidly advancing and changing. This Satellite Symposium offers a forum for sharing of ideas on this subject which may ultimately lead to breakthroughs in understanding the mechanisms of steroid hormone action.

The tuberous electroreceptors of weakly electric fish are related to hair cells of the lateral line and inner ear. Like some hair cells, they are tuned by an electrical filter in their basal membranes. The number of sensory cells in each organ increases throughout the fish's life, the new sensory cells being produced by support cells. Furthermore, after skin has been removed new skin regrows in the wound and tuberous receptor organs regenerate, we believe, from the support cells of intact organs in the surrounding skin that migrate into the regenerating skin. During regeneration the tuberous organ begins as a layer of support cells around a lumen, and these support cells also give rise to the new sensory cells. These receptors show a dependence on their innervation in that receptor organs become disrupted and lose sensory receptor cells 2-3 weeks after denervation. Receptor organs also do not appear in denervated skin. We wish to answer the following questions in this proposal. 1) Does receptor cell tuning change after denervation? 2) What morphological changes occur in receptors as they degenerate and what changes, if any, occur in the support cells? 3) What role does innervation play in stimulating support cells to become mitotic and add new sensory cells in intact organs? 4) What role does innervation play in the early regeneration of tuberous sensory organs and, do organs regenerate if the new skin is surrounded by old organs that are denervated? 5) Are newly regenerated organs especially sensitive to denervation? 6) How do rates of mitosis change in support cells of regenerating organs after denervation? The results from this study will increase our fundamental understanding of the process of sensory cell regeneration and the putative trophic influence of afferent nerves upon their sensory cells.

[unreadable] DESCRIPTION (provided by applicant): The electrical excitability of nerve, muscle, heart, and other cells depends on ion channels. Mutations of ion channels cause a number of inherited diseases. Understanding how ion channels are regulated is an important basic and clinical science goal. We propose to use the communication signals of a weakly electric fish as a model system to elucidate how ion currents are regulated. The electric organ discharge (EOD) is a sexually dimorphic, hormone-sensitive, and individually distinct communication signal. The wave shape of the EOD is intimately dependent on and reflective of the membrane properties of the cells in the electric organ because these signals are in the currency of the nervous system--electricity. We have shown that the wave shape of the EOD pulse is determined by Na+ and K+ currents and that the biophysical properties of these currents are sexually dimorphic, individually distinct, and hormonally modulated. In the last granting period we cloned three K+ channel genes from the electric organ and observed that two of them are expressed in high levels in females and low levels in males, and that their levels are suppressed by androgens. The third is expressed similarly in both sexes and is unaffected by hormones. We also discovered a unique Na+ channel gene. In this proposal we continue to focus on the molecular regulation of the K+ and Na+ currents. Specific aim 1 is to study how the three K+ channel genes generate the observed variation in K+ current kinetics using subunit-specific channel blocking peptides, Western blotting and immunoprecipitaiton, and acolyte injection. Specific aim 2 is to clone and the study the expression and 3ossible hormone regulation of one or more additional candidate K+ channel genes. Specific aim 3 is to: lone and test the possible role of K+ channel beta subunits in regulation of K+ current properties. Specific aim 4 is to study differential expression and hormonal regulation of two splice forms of a Na+ channel beta subunit, and how the different splice forms might influence the inactivation rate of the Na+ current. [unreadable] [unreadable] [unreadable]

In communication systems it is important for the signal and receiver to be matched in the frequency domain to maximize information transfer. Thus, the frequency sensitivity of a species' sensory systems are often matched to the spectrum of that species' communication signal. Nevertheless, little is known about the developmental mechanisms by which output and sensory structures come to be matched or whether they have any capacity for plasticity in mature animals. The match between signal and receiver are extremely precise in those animals that have "active" sensory systems like echolocating bats and electrolocating weakly electric fish. Weakly electric fish are intriguing because the frequency sensitivity of the sensory receptors and the frequency output of the emitter, the electric organ, are not only well matched but both effector and receptor pathways show hormone-mediated plasticity. of prime interest is how the ion currents of the cells in this communication pathway are modulated by hormones. In this proposal we concentrate on hormone induced plasticity of the emitter, the electric organ, where our preliminary data suggest that, variation in and plasticity of a Na+ current is the major determinant of the waveshape properties of its output and the locus of hormone-mediated plasticity. In this proposal we wish to 1) measure additional properties of the Na+ currents (i.e.--I-V curves, steady state inactivation, recovery from inactivation, dissociation constants for TTX and mu conotoxin) to determine if other parameters also vary with electrocyte (a single electric organ cell) spike duration 2) determine whether the kinetics of the delayed rectifying K+ current in electrocytes from fish with a range of EOD frequencies also show individual variation 3) record Na+ currents and K+ currents before and after fish have been treated with androgens or gonadotropin to determine whether the kinetics of these currents can be altered by these hormones 4) determine whether Na+ current kinetics are altered by treatment of the electrocytes with agents that induce phosphorylation of the Na+ channel in other preparations.

AMPA receptors; NMDA receptors; ethology; neural plasticity; neural transmission; biological signal transduction; neurotransmitters; stimulus /response; animal communication behavior; second messengers; gender difference; avoidance behavior; receptor expression; behavioral /social science research tag; fish; fish electric organ; electronic recording system; behavior test; sectioning;

Sensory-motor systems must be recalibrated to adapt to normally-occurring or pathologically-induced changes in the pattern of sensory inputs. For studies of this process, the key questions are pinpointing how the system is appraised of changes in its sensory inputs, and defining the mechanisms by which an adaptive response is generated. This highlights a general problem for excitable cells which is how to scale or vary their responses appropriately with changes in the quantity or pattern of their synaptic inputs. In many cases, critical changes in synaptic activity are communicated to neurons via N-methyl-D- aspartate (NMDA) or metabotropic (mGlu) type glutamate receptors. We propose to use a simple system--the electromotor system of electric fish, which controls the electric organ discharge (EOD)- -to study how alterations in sensory inflow can regulate the activity of motor output circuitry to adaptively change the circuit's and the animal's behavior. These alterations in the sensory inflow are processed in the CNS and ultimately communicated to the pacemaker neurons that control the EOD frequency via NMDA and, possibly, mGlu receptors. Activation of these receptors leads to long-term (many hours) adaptive changes in the firing frequency of these critical pacemaking neurons after the stimulus has ceased. In this proposal we wish to more fully characterize how sensory stimuli induce long-term shifts in motor output (EOD frequency) of behaving animals; identify in a slice preparation how activation of NMDA and mGlu receptors in pacemaking neurons could lead to long-term changes in their postsynaptic firing rates; and, finally, test the role of these receptors in controlling the behavior by blocking them in pacemaking neurons in a restrained behaving animal.

One of the deadliest neurotoxins known is tetrodotoxin (TTX). TTX binds tightly to and blocks sodium channels in muscles, heart, and nerve causing paralysis and death. TTX is of biological origin and is produced by a striking variety of animals such as the blue-ringed octopus, the ghost crab, the California newt, and the pufferfish. In some species TTX is used to capture prey, in others for defense against predation. Because TTX circulates freely in the body of the animals that make it, these animals must evolve insensitivity to their own toxin. Some species of pufferfishes are more toxic than others, and that higher degree of toxicity is matched, obviously, with lower sensitivity of the tissues of those species to the toxin. One hypothesis is that the varying sensitivity of tissues to TTX among these species of pufferfishes likely resides in variation in the amino acid sequences of the proteins associated with the sodium channels. This project focuses on evolution of TTX sensitivity among pufferfishes by way of a mechanistic examination of the evolution of sodium channel proteins.

In order to reconstruct the evolutionary history of the sodium channel genes, the sequences of these genes will be examined from the pufferfish genome database. Next, the genes for three of the six sodium channels will be cloned and sequenced from a variety of related species exhibiting varying degrees of TTX sensitivity. Phylogenetic relationships among the pufferfishes are known. In addition, some related fish with varying degrees of TTX sensitivity, and some unrelated fish that are very sensitive to TTX will be examined. Sensitivity to TTX will be determined by measuring the amount of TTX that binds to tissue samples of brain, muscle and heart. A comparison of the sequences of these sodium channel genes will be made to identify particular amino acids in the sodium channel proteins that are different in those species that are highly insensitive to the toxin versus those that are not. From these data inferences may be drawn to reconstruct how particular mutations accumulated in the 3 genes during the evolutionary history of these species. Thus an understanding of how these genetic mutations influence TTX binding will be gained in the context of current thinking about how the toxin interacts with amino acids in the pore of the sodium channel.

This work on the evolution of pufferfish insensitivity to their own TTX is important for a number of reasons. First, TTX is classified as a weapons-grade toxin. Understanding how animals protect themselves against it may help in designing defense strategies against it. Second, TTX and related compounds are released by marine algae and cause the "red tide" which has a serious impact on fisheries industries and the marine environment. This project will help gain understanding about how some animals can protect themselves against this devastation. Third, because they have small genomes, the genome of the Pufferfish has been cloned and sequenced so there is a wealth of molecular data on this species. The present study will take advantage of that information. Finally, from a theoretical point of view, this is an intriguing question. Fish are known to have six different genes for sodium channels, so TTX sensitivity must have evolved more or less simultaneously in six genes. Understanding how toxin insensitivity evolved in pufferfish will be a model for how animals respond adaptively on a molecular level to environmental challenges. Very few studies have developed the mechanistic links between molecular variation, differential organismal performance, and relative fitness. The present study has great potential to forge those important links.

DESCRIPTION (provided by applicant): Mutations in voltage-dependent sodium channel genes cause neurological, muscular, and cardiac diseases. Although much is known about sodium channel function, there is still much to learn. The sodium channel is a large molecule and understanding which of its many amino acids is important to its function is a daunting task. One method to pinpoint potentially important amino acids in a protein is to align the sequences of the same protein from a number of different organisms to find out which amino acids do NOT change over the course of evolution. Another lesser-used strategy that we employ here is to include sequences from organisms in which that molecule is under strong selection pressure to evolve. In this case, we look for amino acid changes that DO change over the course of evolution. Weakly electric fish generate electric organ discharges (EODs) for communication and sensing objects. EODs are generated by sodium channels and the sodium channels of electric fish have undergone strong selection for species-specific changes in amino acids in critical regions of the channel. Using the approach described above, we have already discovered a novel functional domain of sodium channels. We will continue to study the process of evolution of sodium channel genes in the two independently evolved groups of electric fish in order to discover other functionally important regions of the channel. Using bioinformatics approaches to compare amino acid and nucleotide sequences in the two groups of electric fish, non-electric fish, and other vertebrates, including humans, we will detect amino acids sites that are likely under positive selection in the electric fish's sodium channels. We will then test whether these particular amino acids are truly important to channel function by introducing the amino acid changes that we observe in electric fish sodium channels into a human muscle sodium channel (as well as the converse) and determining whether these alter the biophysical properties of expressed sodium channels. Besides providing insights into the evolutionary processes, this work will aid our basic understanding of the functioning of sodium channels, a clinically important family of ion channels. Project Narrative: Mutations in sodium channel genes cause neurological, muscular, and cardiac diseases. Using bioinformatics approaches we will identify amino acids that are likely to be important to the function of the sodium channel. We will then test whether these particular amino acids are truly important to channel function by perturbing these amino acid in a human muscle sodium channel gene and observing whether these alter the biophysical properties of the sodium channels. This work will be medically important to understand the function of sodium channels, a clinically important family of ion channels.

The 9th International Congress of Neuroethology (ICN) will be held on August 2-7, 2010, in Salamanca, Spain. The ICN is the scientific meeting of the International Society for Neuroethology (ISN) that has been held since 1986. This meeting brings together diverse neuroscientists who investigate the neural basis of behavior across a broad spectrum of animals. It is an outstanding venue to bring together international scientists with a broad range of perspectives, but who all focus on common basic-science questions that have important implications for neural function. Topics include sensory and motor processing, central integrative processes, development, synaptic plasticity and learning, regeneration, and systems-level approaches to understanding plasticity and behavior. In addition some sessions focus on emerging technologies. Neuroethology aims to explain natural behaviors in terms of the activity of individual neurons and networks, and to explore developmental and evolutionary aspects of behavior. Neuroethologists use a comparative approach to seek common solutions to common problems. This involves an understanding of evolutionary principles as they apply to nervous systems and the generation of adaptive behaviors. Evolutionarily informed comparisons of equivalent behaviors in different species can help to identify the common principles that guide the generation of behavior in all species, including humans. The broader impacts of this meeting are to promote engagement in this area for junior investigators, and in particular women and minority scientists, and to stimulate cross-fertilization of ideas among the participants. Support will be directed to fund travel and registration for student, postdoctoral and junior investigators. The benefits to American scientists in general, and to young investigators in particular, will be the opportunity for exposure to cutting-edge research and techniques from around the world.

Understanding the molecular changes by which organisms adapt to their environments is a central theme of evolutionary biology. With the pace of environmental change quickening due to loss of habitat worldwide and accelerated global climate change, and the exposure of humans to previously unencountered pathogens (such as HIV), the processes of molecular evolution are key to our survival and the survival of many organisms on this planet.

This project will study the evolution of resistance to scorpion venom, in ion channels, of desert-dwelling grasshopper mice. Grasshopper mice prey on scorpions and, when stung, show no adverse effects to scorpion venoms that cause intense pain and/or kill other mammals their size. This proposal will focus on the molecular evolution of a sodium ion-channel gene that is expressed in pain-sensing neurons. Species and individual differences in pain sensitivity of grasshopper mice to scorpion venom will be studied on the genetic, physiological and molecular levels, and the consequences of these differences for the behavior and ecology of these unique mice will be determined. This project will also gain further understanding of how the nervous system processes painful stimuli.

This project represents a partnership between the University of Texas, a major research university, and Sam Houston State University, a non-PhD granting institution with many students from underrepresented groups. We will recruit undergraduates from both institutions, focusing on underrepresented minorities. Additionally, this project will produce a videotape on co-evolution with the bark scorpion-grasshopper mouse system as an example of how animals make a living in the harsh desert environment. The videotape will be featured in an exhibit at the Texas Memorial Museum. Finally, our previous work on this system has already attracted interest from the media and there are plans for it to be highlighted in a National Geographic television special.

Why did an ancient duplicate copy of an important muscle gene evolve to become an integral part of a novel organ system used for electrical communication in two families of electric fishes? It is possible that this gene was less essential to muscle than the other duplicate copy of the gene, therefore making it ?easier? for it to evolve a new function in a new cell type. The investigators will measure the patterns of gene expression among several close relatives of the electric fish lineages to determine if expression of this gene changed before it gained a new function in electric fish. This project will also knock out the two genes individually in a close relative of electric fish to determine the relative impact on muscle function. This project will demonstrate how expression evolution may have facilitated functional evolution of this gene.
Gene duplication is the primary source of new genes in a genome and is an important player in the evolution of
novel cells and organ systems. This project seeks to ascertain the sequence of events that led to the evolution of a novel function for a duplicate gene which made it functionally distinct from the ancestral gene. This will provide insights into the molecular mechanisms behind gene evolution after duplication and how that relates to the evolution of novel organ systems. The project also provides research training to several undergraduate students, and the co-PI will promote findings of the project through a public website demonstrating evolution through simulations.

This project studies how the proteins of the nerves and muscles of fish that live in Antarctica function in the cold, which should provide information on the function of these same proteins in all animals, including humans. These proteins, called ion channels, open and close to allow ions (atoms or molecules with electrical charge) to flow into or out of cells which causes the electrical activity of nerves and muscles. Mutations that influence this process are the basis of numerous human disorders such as epilepsy, heart arrhythmias, and muscle paralysis. Thus, it is important to understand what parts of the proteins govern these transitions. The speed with which channels open and close depends on temperature. Human ion channels transition slowly when we are cold, which is why we become numb in the cold. Yet Antarctic fish, called icefish, are active at freezing temperatures that drastically limit the activity of human ion channels. The investigators have evidence that specific alterations in the icefishs' ion channels allow their channels to operate differently in the cold and they will use gene discovery and biophysical methods to test how these changes alter the transitions of icefish proteins at different temperatures. The project will also further the NSF goals of training new generations of scientists and of making scientific discoveries available to the general public. The gene discovery analysis will be done by undergraduate students including those from a minority-serving university and the investigators will develop a new course which will also serve students at that institution and elsewhere. In addition, the investigators will participate in educational outreach events with the general public as well as with groups with special needs.

Notothenioid fishes are one of the most successful groups of vertebrates in Antarctica. Notothens have adaptations to the freezing water they inhabit and this project will study how their voltage-gated ion channels (VGICs) function in the cold. The molecular movements of ion channels are severely impaired by cold, yet notothens function at temperatures that would paralyze the nerves and muscles of "cold-blooded" temperate zone animals. Surprisingly, no biophysical or molecular investigations have been conducted on notothen VGICs. The investigators have preliminary data that amino acid substitutions occur at sites in VGICs that are evolutionarily conserved from fruit flies to humans. Some of these sites are known to impact channel function and the role of others in channel transitioning are unknown. The results from studying them will provide novel information also applicable to non-notothen, perhaps even human, VGICs as well as providing insights into how VGICs adapt to the cold. The project will biophysically characterize notothen VGICs using voltage-clamp techniques will and compare their properties over a range of temperatures to the same channel from two temperate zone fish. The role of unique notothen amino acid substitutions will be characterized by mutagenesis. One specific aim will be a project in which undergraduates mine notothen sequence databases to identify other potential amino acid substitutions in VGICs that might facilitate adaptation to the cold.

Ion channels, specialized proteins that reside in the cell membrane, shape the electrical activity of nervous systems in all forms of life. Naturally occurring variation (mutations) in genes that encode ion channel proteins can determine electrical properties throughout the nervous system. To better understand the relationship between sequence, structure and function of ion channels, the investigators will use mutations discovered in a potassium channel gene found only among the weakly electric fishes of Africa. They hypothesize that these mutations confer extraordinarily rapid molecular movements, and thus rapid electrical activity, enabling these fishes to produce rapid pulses of electricity used in communication and navigation. The first aim of this grant will be to sequence this gene from a variety of African electric fishes to determine the evolutionary origin of this mutation. The second aim will be to express these genes in-vitro to investigate the physical properties that the mutation confers. This work is important because it gives us greater insight into the role that genetic changes play in determining electrical properties of all types of cells, including heritable diseases of the nervous system (channelopathies), as well as adaptive differences that may shape the nervous system in the evolution of new behaviors. As part of their work, the investigators will train undergraduates, including those from underrepresented groups in science, through coursework and laboratory experiences in molecular evolution, physiology and genomics.

Investigators will investigate the relationship between sequence evolution and biophysical properties of a potassium channel (Kv) exclusively expressed in the electric organ, a derivative of muscle, in African electric fish. Most electric organ discharges (EODs), are used for communication and navigation, and are extraordinarily brief (500 microseconds) within this group, however a few species have secondarily evolved long duration discharges. One Kv channel (kcna7a) is abundantly expressed in the electric organ, and preliminary data suggests high rates of sequence evolution and amino acid substitutions in otherwise highly conserved regions of this protein, likely conferring unique biophysical properties. In the first aim investigators will perform RNAseq on electric organ and muscle tissues from 10 species of African electric fish strategically chosen for their phylogenetic relationships and waveform duration, and examine kcna7a sequence evolution as it relates to EOD phenotypic evolution. In the second aim, investigators will perform site-directed mutagenesis on kcna7a channel genes, guided by discoveries in aim 1, express mutagenized channels in frog oocytes, and perform physiological recordings to determine biophysical properties conferred by specific amino acids. This work will give insights into the genetic basis of rapid evolution of a communication signal involved in speciation; investigate novel amino acid substitutions in a class of medically-relevant ion channels that are universally important in shaping neural activity; potentially provide resources for making channels with hyper-fast kinetics for shaping electrical activity in tissue engineering and provide transcriptomic resources for laboratories studying other aspects of electric organ development and evolution.