GABAA single-channel conductance is set by the GABA concentration in outside-out patches from hippocampal neurons

GABAA single-channel conductance is set by the GABA concentration in outside-out patches from hippocampal neurons

Field: Neurotransmitters and receptors

Authors: Birnir, Bryndis
Eghbali, Mansoureh
Cox, Graeme B
Gage, Peter W

Address of presenting
author: Bryndis Birnir
Dept of Physiological Sciences
Sölvegatan 19
Lund University

E-mail: bryndis.birnir@mphy.lu.se

Phone: 222 0633

Fax: 222 7763

Text of abstract: GABAA SINGLE-CHANNEL CONDUCTANCE IS SET BY THE GABA CONCENTRATION IN OUTSIDE-OUT PATCHES FROM CULTURED HIPPOCAMPAL NEURONS.

Bryndis Birnir¹, Mansoureh Eghbali², Graeme B. Cox² & Peter W. Gage². ¹Dept. of Physiological Sciences, Lund University, Sweden. ²John Curtin School of Medical Research, Australian National University, Canberra, Australia

The inhibitory GABAA receptor is thought to be the target for many clinically useful drugs such as general anaesthetics, barbiturates, benzodiazepines and anti-epileptics, all of which can potentiate GABA currents. We have been studying GABAA channels in outside-out patches in rat cultured hippocampal neurons. As observed previously in hippocampal slices (Birnir et al., 1994) channel conductance increased with GABA concentration and was decreased by bicuculline. The GABA activation curve of single-channel conductance gave an EC50 value of about 30 mM. When 10 mM GABA was applied to a patch, channels with conductance up to 120 pS were activated. A progressive increase in bicuculline concentration resulted in a progressive decrease in conductance of single channels activated by 100 mM GABA and gave a bicuculline IC50 of about 19 mM. Both the GABA EC50 value and the bicuculline IC50 value are comparable to those reported from whole-cell current measurements. Benzodiazepines, a widely used family of anxiolytic drugs, enhance neuronal inhibition mediated by GABA in the central nervous system and this has been correlated with an increase in the open probability of GABAA channels. We have found that diazepam can increase the conductance of GABAA channels (Eghbali et al.,1997) and in the presence of 1 mM diazepam the GABA EC50 value was shifted to about 0.2 mM. An important effect of neurotransmitters and drugs on ion channels may be modulation of channel conductance.

Birnir, B, Everitt, A. & Gage, P.W. (1994) J. Membrane Biol 142, 93-102.
Eghbali, M. Curmi, J., Birnir, B. & Gage, P.W.(1997) Nature., 388: 71-75.

Keywords: GABA, GABAA receptors, Inhibition, Anaesthetics

	GABAA single-channel conductance is set by the GABA concentration in outside-out patches from hippocampal neurons
Field:	Neurotransmitters and receptors
Authors:	Birnir, Bryndis Eghbali, Mansoureh Cox, Graeme B Gage, Peter W
Address of presenting author:	Bryndis Birnir Dept of Physiological Sciences Sölvegatan 19 Lund University
E-mail:	bryndis.birnir@mphy.lu.se
Phone:	222 0633
Fax:	222 7763
Text of abstract:	GABAA SINGLE-CHANNEL CONDUCTANCE IS SET BY THE GABA CONCENTRATION IN OUTSIDE-OUT PATCHES FROM CULTURED HIPPOCAMPAL NEURONS. Bryndis Birnir¹, Mansoureh Eghbali², Graeme B. Cox² & Peter W. Gage². ¹Dept. of Physiological Sciences, Lund University, Sweden. ²John Curtin School of Medical Research, Australian National University, Canberra, Australia The inhibitory GABAA receptor is thought to be the target for many clinically useful drugs such as general anaesthetics, barbiturates, benzodiazepines and anti-epileptics, all of which can potentiate GABA currents. We have been studying GABAA channels in outside-out patches in rat cultured hippocampal neurons. As observed previously in hippocampal slices (Birnir et al., 1994) channel conductance increased with GABA concentration and was decreased by bicuculline. The GABA activation curve of single-channel conductance gave an EC50 value of about 30 mM. When 10 mM GABA was applied to a patch, channels with conductance up to 120 pS were activated. A progressive increase in bicuculline concentration resulted in a progressive decrease in conductance of single channels activated by 100 mM GABA and gave a bicuculline IC50 of about 19 mM. Both the GABA EC50 value and the bicuculline IC50 value are comparable to those reported from whole-cell current measurements. Benzodiazepines, a widely used family of anxiolytic drugs, enhance neuronal inhibition mediated by GABA in the central nervous system and this has been correlated with an increase in the open probability of GABAA channels. We have found that diazepam can increase the conductance of GABAA channels (Eghbali et al.,1997) and in the presence of 1 mM diazepam the GABA EC50 value was shifted to about 0.2 mM. An important effect of neurotransmitters and drugs on ion channels may be modulation of channel conductance. Birnir, B, Everitt, A. & Gage, P.W. (1994) J. Membrane Biol 142, 93-102. Eghbali, M. Curmi, J., Birnir, B. & Gage, P.W.(1997) Nature., 388: 71-75.

Keywords:	GABA, GABAA receptors, Inhibition, Anaesthetics

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Created 2000-03-15

Department of Physiological Sciences, Lund University

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