Changes in intracellular calcium concentration affect desensitization
kinetics of GABAA receptors in acutely dissociated P2-P6 rat hippocampal
neurons.
Jerzy W. Mozrzymas and Enrico Cherubini.
Biophysics Sector and Istituto Nazionale Fisica della Materia Unit,
International School for Advanced Studies (SISSA), Via Beirut 2-4, 34014
Trieste, Italy
APStracts 4:305N, 1997.
ABSTRACT
The whole-cell configuration of the patch clamp technique was used to study
the effects of different cytosolic calcium concentrations [Ca2+]i on
desensitization kinetics of ë-aminobutyric acid (GABA)- activated receptors in
acutely dissociated rat hippocampal neurons. Two different intrapipette
concentrations of the calcium chelator BAPTA (11 and 0.9 mM, respectively)
were used to yield a low (1.2ù10-8M) or a high (2.2ù10-6M) [Ca2+]i. In low
[Ca2+]i, peak values of GABA-evoked currents (20 æM) evoked at -30 mV, were
significantly larger than those recorded in high calcium (2970 ñ 280 pA versus
1870 ñ 150 pA). The extent of desensitization, assessed from steady-state to
peak ratio was significantly higher in high calcium conditions (0.14 ñ 0.007
versus 0.11 ñ 0.008). Similar effects of [Ca2+]i on desensitization were
observed with GABA (100 æM). Recovery from desensitization, measured at 30 s
interval with double pulse protocol was significantly slower in high [Ca2+]i
than in low [Ca2+]i (54 ñ 3 % versus 68 ñ 2 %). The current/voltage
relationship of GABA-evoked currents was linear in the potential range between
-50 and +50 mV. The kinetics of desensitization process including the rate of
onset, extent of desensitization and recovery were voltage-independent.
Run down of GABA-evoked currents was faster with the higher intracellular
calcium concentration. The run down process was accompanied by changes in
desensitization kinetics: in both high and low [Ca2+]i, desensitization rate
was progressively increasing with time as the slow component of the
desensitization onset was converted into the fast one.
In excised patches, the desensitization kinetics was much faster and more
profound than in the whole-cell configuration, indicating the involvement of
intracellular factors in regulation of this process.
In conclusion, [Ca2+]i affects the desensitization of GABAA receptors possibly
by activating calcium-dependent enzymes that regulate their phosphorylation
state. This may lead to modifications in cell excitability due to changes in
GABA-mediated synaptic currents.
Received 2 June 1997; accepted in final form 29 October 1997.
APS Manuscript Number J454-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997