| Type of Document |
Dissertation |
| Author |
Artim, Debra Elaine
|
| URN |
etd-04212005-121742 |
| Title |
Activation of Voltage-gated Calcium Current by Action Potentials and Modulation by G Proteins |
| Degree |
Doctor of Philosophy |
| Program |
Neuroscience |
| School |
School of Arts and Sciences |
| Advisory Committee |
| Advisor Name |
Title |
| David Wood |
Committee Chair |
| Alison Barth |
Committee Member |
| Guoqiang Bi |
Committee Member |
| Jon Johnson |
Committee Member |
| Stephen D. Meriney |
Committee Member |
| Stephen Jones |
Committee Member |
|
| Keywords |
- voltage dependence
- ciliary ganglion
- somatostatin
|
| Date of Defense |
2005-02-23 |
| Availability |
unrestricted |
Abstract
Voltage-gated calcium channels are ubiquitously expressed in neurons and are of vital importance to proper cellular functioning. Calcium entry into cells via activation of voltage-gated calcium channels controls a wide variety of cellular functions including neurotransmitter release, muscle excitation-contraction coupling, gene regulation and activation of signaling cascades. Regulation of calcium channels via activation of G protein-coupled receptors is a prominent mechanism of calcium current inhibition and neurotransmitter release. An intriguing characteristic of this modulatory pathway is its voltage dependence whereby the degree of calcium current inhibition varies depending on the membrane voltage of the cell, and is susceptible to activity-dependent relief by trains of action potentials. Previously, it has been suggested that in chick ciliary ganglion neurons, somatostatin inhibits calcium current in a voltage dependent manner. Interestingly, the specific characteristics of the inhibition varied depending on the recording configuration used to collect data. Thus, I measured the voltage-dependence of somatostatin-mediated calcium current inhibition in individual ciliary ganglion neurons using the whole-cell and perforated patch configuration of voltage clamp recordings. The results indicate that the cytoplasmic dialysis that occurs during whole-cell recordings enhances the voltage dependence of calcium current inhibition and suggests that there is a greater concentration of activated G protein subunits in this configuration. While much is known about step depolarization-evoked calcium current and the kinetic changes that accompany G protein-mediated inhibition, relatively little is known about the effects of kinetic slowing on AP-evoked calcium current. Therefore, I used a modification of action potential waveforms was used to determine the effect of G protein activation on the kinetics of single action potential-evoked calcium current. The results demonstrate that kinetic slowing does not alter the time course of action potential-evoked calcium current and suggests that modulated channels may not contribute to AP-evoked calcium current.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
|
| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
| |
DEArtim2005.pdf |
41.54 Mb |
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01:38:54 |
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