Clay M. Armstrong - US grants

Experiments will be performed on four preparations to gain a better understanding of the widespread phenomenon of excitability, which is a property of nerve, muscle, heart, endocrine, and other cells. The Na and K channels of never membrane will be examined in internally perfused, voltage clamped squid giant axons. The basic techniques will be measurement of ionic current, gating current, current fluctuations, and single channel currents. One objective is to devise a kinetic model that harmonizes information derived form all of these techniques. In addition, chemical probes which interact with the channels or their gating machinery will be used, including a variety of drugs, dyes, and mono and divalent cations. The effect of temperature will be examined, with particular attention to a dramatic change in Na channel properties that occurs at low temperature. The electrical properties of cerebral cortical pyramidal cells will be examined in vitro using the brain slice technique. Among our goals are a direct measurement of the space constant of apical dendrites, determination of the excitability properties of soma and dendrites, and characterization of the permeabilities responsible for excitability. The suitability of the first order giant cell in the squid as a physiological preparation will be ascertained. This preparation should be advantageous for the study of soma and denditic properties, and may be useful as a synaptic preparation. The electrical properties of the parathyroid gland will be investigated, with the major objectives of characterizing its electrical activity if any, relating this activity to secretion, and determining the mechanism by which changes of the serum calcium concentration are transduced into electrical activity.

A symposium covering the topic of secretion and its control is planned, to be held at the Marine Biological Laboratory in Woods Hole, Massachussetts, Sept. 7-11, 1988. The symposium will be sponsored by the Society of General Physiologists, and will be the Society's 35th annual symposium. Under the central theme of secretion and its control, consideration will be given to a wide variety of questions, tissues, and techniques, from production and routing of secretory products to the mechanism of exocytosis, from viruses to endocrine tissues, and from cell biology to biophysics. The major areas to be covered are the following. Cell Biological Insights into the Secretory Process. This will include discussions of intracellular protein traffic and targeting; how secreted substances are packaged in vesicles; fusion of viruses with cells and organelles (perhaps a model for exocytosis); endocytosis and clathrin; and the movement of subcellular particles and vesicles. Cell Surface Receptors and Second Messengers, including discussions of the structure and activity of cell surface receptors and second messenger systems involved with the control of secretion. The role of Electrical Phenomena in Secretory Control, including discussions of spontaneous pacemaking activity and its influence on insulin secretion in pancreatic islet and pituitary cells. Calcium and Calcium Channels, with discussions of their role in controlling secretion, and an examination of possible alternate means of secretory control that do not involve calcium. Exocytosis, with discussion of biophysical, biochemical, and physicochemical approaches to understanding of the fusion process and exocytosis, 29 speakers have been invited, including 3 speakers from abroad. In addition there will be poster sessions which will contain predominantly work related to secretion. The program will consist of five lecture-discussion periods, each of approximately four hours duration. A full afternoon will be devoted to each of the poster sessions. There will be no overlapping sessions. Dr. Michael S. Brown has agreed to be the keynote speaker for the symposium.