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High-probability grants
According to our matching algorithm, Paul Horowicz is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
1985 — 1987 |
Horowicz, Paul |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Inward Rectifier and Na+ -K+ Pump in Skeletal Muscle @ University of Rochester
One aim of this research project is to characterize in detail the ionic flux and the current-voltage relations of the potassium inward rectifier in frog striated muscle fiber. The inward rectifier is located in the muscle membranes covering the external surface and those of the transverse tubular system. It is the major ionic pathway controlling the membrane potential and indirectly, other electrical properties of striated muscle under resting conditions. This rectifier system will be studied in cut single fibers under controlled membrane potentials where both the internal and external potassium ion concentrations can be varied. The effects of other alkali metal ions, such as rubidium and caesium, which both activate and block potassium movements through the rectifier will be studied. The modifications produced by various other agents such as hydrogen ions, barium, quaternary ammonium ions and various group specific chemical agents on this conductance system will also be studied. The entry of sodium and the loss of potassium through the inward rectifier is offset by the parallel action of the Na plus K plus exchange pump. Our other major aim is to better characterize this pump in skeletal muscle. The major fraction of the pump sites in muscle is located on the external surface and only a small fraction in the transverse tubular system. The Na[unreadable]+[unreadable] K[unreadable]+[unreadable] pump will also be studied in cut single fibers under controlled membrane potentials where the internal and external concentrations of both sodium and potassium can be varied as well as the levels of internal ATP and ADP. The parallel operation of these two systems determines the resting steady state distribution of Na plus and K plus and the resting membrane potential. The propertis of these systems are probably among the chief factors involved in hypotension and skeletal muscle weakness associated with hypokalemia and the paralysis of skeletal muscle associated with hyperkalemia.
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1 |
1987 |
Horowicz, Paul |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Renal Substrate Utilization in Relation to Function @ University of Rochester
The objectives of the proposed studies are to gain a more complete understanding of how Na+ excretion and conservation are regulated in the intact kidney and how the metabolism of substrates are linked to these regulatory mechanisms in normal and diseased kidneys. In particular we wish to determine whether the metabolism of glucose selectively provides the energy for support of Na+ reabsorption along the distal portion of the nephron. Since, in this region of the nephron hormones such as insulin, anti-diuretic hormone, aldosterone and norepinephrine as well as the "cardiac atrial natriuretic factor" manifest their action, we also will determine whether, when these mediators are present, there are simultaneous changes in the metabolism of glucose and in Na+ excretion. In order to define the metabolic and hormonal mechanisms which are linked to regulation of Na+ reabsorption we will do these studies with the isolated perfused rat kidney. In this preparation no neural or hormonal phenomena and the influence of other organs on renal function and metabolism are virtually absent. Therefore we can introduce each of these variables in controlled fashion. Similarly we can regulate the availability of glucose or other substrates to the kidney so that the discrete role of a substrate in permitting regulation of Na+ conservation can be determined. Thus from the simultaneous measurements of function and metabolism in kidneys from normal or from diseased (e.g. diabetes) animals we will be able to gain a more complete understanding of regulation of Na+ conservation.
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1 |
1988 — 1992 |
Horowicz, Paul |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ionic Properties of Skeletal Muscle Membranes @ University of Rochester
The membrane mechanisms resulting in the movements of K+ and Cl- in normal skeletal muscle fibers of the frog are being studied. These two ions account for most of the membrane conductance in quiescent muscle fibers. In resting muscle the major passive pathway for K+ movement is the inward rectifier channel while the major pathway for Cl- movement is the external pH dependent Cl- channel. The pH dependent chloride channels in frog skeletal muscle appear to be principally located in the external surface of muscle cells with few such channels present in the membranes lining the transverse tubular system. Transmembrane chloride fluxes increase markedly when external pH is increased from 5.0 to 10.0 with a midpoint at about pH 6.8. The effects of external chloride concentration, membrane potential, and group specific chemical reagents on the pH dependence of chloride movements will be examined. In addition, the effects on Cl- movements of inorganic anions of the lyotropic series and various aromatic carboxylic acids will be studied at various external pHs, (Cl-)o, and membrane potentials and after chemical modification. The inward rectifier channels are located in the membranes covering the external surface of muscle cells as well as those lining the transverse tubular system. They provide the principal control for steady state membrane potential and, indirectly, other electrical properties of striated muscle under resting conditions. The rectifier channels will be studied in (1) whole sartorius muscles and in (2) single fibers under controlled membrane potentials where both the internal and external concentrations of different ions can be varied. The effects of other ions, such as Rb+ and Tl+, which both activate and inhibit potassium movements through the rectifier as well as moving through the rectifier channels themselves, will be studied. The modifications produced by various agents (i.e. quaternary onium ions) on this channel system will also be explored. The properties of the K+ inward rectifier are among the factors involved in hypotension and skeletal muscle weakness associated with hyperkalemia. Alteration of membrane conductance to chloride ions is one of the factors involved in some myotonias.
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1 |