Abstract

The long term goal of this work is to understand the mechanisms that generate neuronal activity, and modulation of that activity by neurotransmitters. The first step is characterization of the voltage- dependent ion channels of frog sympathetic neurons, using whole-cell and single channel patch clamp techniques. These cells are particularly favorable for voltage clamp studies, and much is already known about the channels underlying electrical activity in sympathetic neurons. A major part of the project will involve study of the voltage-dependent calcium channels, and comparison of those channels to calcium channels in other cell types. Kinetic models of the behavior of calcium and other channels will be developed, to construct a computer model of electrical activity in these cells. The model will be tested by comparing action potentials, and patterns of action potentials, generated by the model to those actually produced by sympathetic neurons. This analysis of the normal behavior of the cell will be supplemented by study of the effects of neurotransmitters on the preexisting voltage-dependent currents. One goal is to explain quantitatively the increased excitability of frog sympathetic neurons induced by slow synaptic potentials.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS024471-05
Application #
3409143
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-04-01
Project End
1995-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Lopin, Kyle V; Gray, I Patrick; Obejero-Paz, Carlos A et al. (2012) Feýýýýý block and permeation of CaV3.1 (ýý1G) T-type calcium channels: candidate mechanism for non-transferrin-mediated Feýýýýý influx. Mol Pharmacol 82:1194-204
Jones, Stephen W; Friel, David D (2006) The amplitude distribution of release events through a fusion pore. Biophys J 90:L39-41
Obejero-Paz, Carlos A; Gray, I Patrick; Jones, Stephen W (2004) Y3+ block demonstrates an intracellular activation gate for the alpha1G T-type Ca2+ channel. J Gen Physiol 124:631-40
Jones, Stephen W (2003) Calcium channels: unanswered questions. J Bioenerg Biomembr 35:461-75
Frazier, C J; Serrano, J R; George, E G et al. (2001) Gating kinetics of the alpha1I T-type calcium channel. J Gen Physiol 118:457-70
Serrano, J R; Dashti, S R; Perez-Reyes, E et al. (2000) Mg(2+) block unmasks Ca(2+)/Ba(2+) selectivity of alpha1G T-type calcium channels. Biophys J 79:3052-62
Frazier, C J; George, E G; Jones, S W (2000) Apparent change in ion selectivity caused by changes in intracellular K(+) during whole-cell recording. Biophys J 78:1872-80
Serrano, J R; Perez-Reyes, E; Jones, S W (1999) State-dependent inactivation of the alpha1G T-type calcium channel. J Gen Physiol 114:185-201
Kammermeier, P J; Jones, S W (1998) Facilitation of L-type calcium current in thalamic neurons. J Neurophysiol 79:410-7
Block, B M; Stacey, W C; Jones, S W (1998) Surface charge and lanthanum block of calcium current in bullfrog sympathetic neurons. Biophys J 74:2278-84

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