G-Protein activation mediates prepulse facilitation of Ca2+ channel currents in bovine chromaffin cells |
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Authors: | C. A. Doupnik R. Y. K. Pun |
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Affiliation: | (1) Department of Physiology and Biophysics, University of Cincinnati College of Medicine, 45267-0576 Cincinnati, Ohio;(2) Present address: Division of Biology 156-29, California Institute of Technology, 91125 Pasadena, California |
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Abstract: | The effects of G-protein activation were investigated on tonic, large depolarization-induced Ca2+ channel facilitation in cultured bovine adrenal chromaffin cells. Under whole-cell voltage clamp, activation of G proteins by intracellular dialysis with 200 M GTP-S did not significantly affect prepulse facilitation or whole-cell Ba2+ current (IBa) density. In contrast, inactivation of G proteins by intracellular GDP-S or pertussis toxin (PTX) pretreatment completely abolished or markedly attenuated facilitation of IBa, respectively. GDP-S dialysis resulted in nearly a threefold increase in peak IBa density, whereas PTX pretreatment resulted in a 50% increase. Our results indicate that under control recording conditions (200 m intracellular GTP), G proteins are tonically activated and suppress high-voltage-activated (HVA) Ca2+ channels in a voltage-dependent and voltage-independent manner. Local superfusion of chromaffin cells with normal bath solution produced a rapid and reversible increase (50%) in IBa amplitudes that also abolished prepulse facilitation. Together, these results demonstrate that tonic facilitation of HVA Ca2+ channels in bovine chromaffin cells involves the voltage-dependent relief of a G-protein-mediated suppression, imposed by chromaffin cell secretory products that feedback and activate G-protein-coupled autoreceptors.This work was supported by a National Science Foundation grant (DCB-8812562), American Heart Association-Ohio Affiliate grant (SW-91-18), and an American Parkinson's Disease Association grant. C.A.D. was supported by a predoctoral National Research Service Award (National Institutes of Health training grant HL07571-08). The authors thank Kluener's Packing Co. for their generous supply of adrenal glands. |
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Keywords: | Ca channel Facilitation G protein Chromaffin cell Bovine Whole-cell patch clamp |
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