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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Physiology Study Section (PHY)
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University of Pennsylvania
Schools of Medicine
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Gomez-Lagunas, Froylan; Melishchuk, Alexey; Armstrong, Clay M (2003) Block of Shaker potassium channels by external calcium ions. Proc Natl Acad Sci U S A 100:347-51
Armstrong, Clay M (2003) The Na/K pump, Cl ion, and osmotic stabilization of cells. Proc Natl Acad Sci U S A 100:6257-62
Armstrong, C M; Cota, G (1999) Calcium block of Na+ channels and its effect on closing rate. Proc Natl Acad Sci U S A 96:4154-7
Armstrong, C M (1999) Distinguishing surface effects of calcium ion from pore-occupancy effects in Na+ channels. Proc Natl Acad Sci U S A 96:4158-63
Armstrong, C M; Hille, B (1998) Voltage-gated ion channels and electrical excitability. Neuron 20:371-80
Khodakhah, K; Melishchuk, A; Armstrong, C M (1998) Charge immobilization caused by modification of internal cysteines in squid Na channels. Biophys J 75:2821-9
Melishchuk, A; Loboda, A; Armstrong, C M (1998) Loss of shaker K channel conductance in 0 K+ solutions: role of the voltage sensor. Biophys J 75:1828-35
Khodakhah, K; Melishchuk, A; Armstrong, C M (1997) Killing K channels with TEA+. Proc Natl Acad Sci U S A 94:13335-8
Mathes, C; Rosenthal, J J; Armstrong, G M et al. (1997) Fast inactivation of delayed rectifier K conductance in squid giant axon and its cell bodies. J Gen Physiol 109:435-48
Khodakhah, K; Armstrong, C M (1997) Inositol trisphosphate and ryanodine receptors share a common functional Ca2+ pool in cerebellar Purkinje neurons. Biophys J 73:3349-57

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