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Activation of a Large‐conductance Ca 2+ ‐Dependent K + Channel by Stimulation of Glutamate Phosphoinositide‐coupled Receptors in Cultured Cerebellar Granule Cells

Activation of a Large‐conductance Ca 2+ ‐Dependent K + Channel by Stimulation of Glutamate... Trans‐1‐amino‐cyclopentyl‐1,3‐dicarboxylic acid (trans‐ACPD), a specific agonist of the glutamate phosphoinositide‐coupled receptor (Qp receptor), increased the amplitude of the outward K+ current recorded in the whole‐cell configuration of the patch‐clamp technique in mouse cultured cerebellar granule cells. This effect was abolished by buffering internal Ca2+ with BAPTA (1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid). Activation of a large‐conductance K+ channel was observed when trans‐ACPD or quisqualic acid (QA), another Qp receptor agonist, was applied outside the cell‐attached patch pipettes. No activation was observed with alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), a specific agonist of ionotropic non‐N‐methyl‐d‐aspartate (non‐NMDA) receptors. The effects of trans‐ACPD or QA were potentiated in the presence of external Ca2+. The channel was also directly activated by both micromolar concentrations of internal Ca2+ and membrane depolarization. Its unitary conductance was 100–115 pS under asymmetrical K+ and 195–235 pS under high symmetrical K+ conditions. In the absence of agonist, the channel was blocked by 1 mM external tetraethylammonium. This is the first description of a large conductance Ca2+‐activated K+ channel in cultured cerebellar granule cells. It possesses properties similar to those of the so‐called ‘big K+ channel’ described in other preparations. Our cell‐attached experiments demonstrated an indirect coupling between Qp receptors and this channel. The most likely hypothesis is that the second messenger system inositol 1,4,5‐triphosphate (IP3)‐Ca2+ was involved in the coupling process. This hypothesis was further strengthened by our whole‐cell experiments. On the basis of the voltage‐ and Ca2+‐sensitivities of the studied channel, we estimated an increase of 350 to 570 nM in internal Ca2+ concentration when Qp receptors were stimulated by 100 μM trans‐ACPD. Under physiological conditions, stimulation of Qp receptors by the endogenous neurotransmitter should lead to similar K+ channel activation and therefore would tend to reduce the efficacy of ionotropic glutamate synaptic receptor stimulation responsible for cell excitation. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Activation of a Large‐conductance Ca 2+ ‐Dependent K + Channel by Stimulation of Glutamate Phosphoinositide‐coupled Receptors in Cultured Cerebellar Granule Cells

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References (64)

Publisher
Wiley
Copyright
Copyright © 1991 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1111/j.1460-9568.1991.tb01674.x
Publisher site
See Article on Publisher Site

Abstract

Trans‐1‐amino‐cyclopentyl‐1,3‐dicarboxylic acid (trans‐ACPD), a specific agonist of the glutamate phosphoinositide‐coupled receptor (Qp receptor), increased the amplitude of the outward K+ current recorded in the whole‐cell configuration of the patch‐clamp technique in mouse cultured cerebellar granule cells. This effect was abolished by buffering internal Ca2+ with BAPTA (1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid). Activation of a large‐conductance K+ channel was observed when trans‐ACPD or quisqualic acid (QA), another Qp receptor agonist, was applied outside the cell‐attached patch pipettes. No activation was observed with alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), a specific agonist of ionotropic non‐N‐methyl‐d‐aspartate (non‐NMDA) receptors. The effects of trans‐ACPD or QA were potentiated in the presence of external Ca2+. The channel was also directly activated by both micromolar concentrations of internal Ca2+ and membrane depolarization. Its unitary conductance was 100–115 pS under asymmetrical K+ and 195–235 pS under high symmetrical K+ conditions. In the absence of agonist, the channel was blocked by 1 mM external tetraethylammonium. This is the first description of a large conductance Ca2+‐activated K+ channel in cultured cerebellar granule cells. It possesses properties similar to those of the so‐called ‘big K+ channel’ described in other preparations. Our cell‐attached experiments demonstrated an indirect coupling between Qp receptors and this channel. The most likely hypothesis is that the second messenger system inositol 1,4,5‐triphosphate (IP3)‐Ca2+ was involved in the coupling process. This hypothesis was further strengthened by our whole‐cell experiments. On the basis of the voltage‐ and Ca2+‐sensitivities of the studied channel, we estimated an increase of 350 to 570 nM in internal Ca2+ concentration when Qp receptors were stimulated by 100 μM trans‐ACPD. Under physiological conditions, stimulation of Qp receptors by the endogenous neurotransmitter should lead to similar K+ channel activation and therefore would tend to reduce the efficacy of ionotropic glutamate synaptic receptor stimulation responsible for cell excitation.

Journal

European Journal of NeuroscienceWiley

Published: Aug 1, 1991

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