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Voltage‐dependent deactivation and desensitization of GABA responses in cultured murine cerebellar granule cells
Author(s) -
Mellor J. R.,
Randall A. D.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.377bw.x
Subject(s) - depolarization , biophysics , membrane potential , chemistry , nipecotic acid , desensitization (medicine) , tetrodotoxin , electrophysiology , gabaergic , reversal potential , neuroscience , gamma aminobutyric acid , biology , patch clamp , receptor , biochemistry , neurotransmitter
1 Electrophysiological recordings of GABAergic IPSCs and responses to applications of exogenous GABA were made from cultured murine cerebellar granule cells. In both the presence and absence of tetrodotoxin, depolarization of the postsynaptic cell consistently produced a broadening of the IPSC. This voltage‐dependent change in kinetics arose entirely from a slowing of the rate of current decay. The duration of miniature IPSCs was increased by a significant but lesser amount by the GABA uptake inhibitor nipecotic acid (300 μM). 2 Five millisecond applications of 1 mM GABA elicited rapidly activating, biexponentially deactivating currents in patches derived from granule cell bodies. Deactivation of these responses was slowed by membrane depolarization. This effect arose from an increased fractional participation of the slow component of deactivation. The benzodiazepine flunitrazepam (1 μM) slowed deactivation at a holding potential of −70 mV but not at +50 mV. 3 Longer‐lasting applications of GABA produced substantial biexponential macroscopic desensitization. The rate of desensitization was faster at a holding potential of +50 mV than at −70 mV. The speeding of desensitization at depolarized membrane potentials arose from an increase in the fractional contribution of the fast component of desensitization. 4 When two 5 ms, 1 mM GABA applications were made at an interstimulus latency of 150 ms, the second response was consistently smaller than the first. The depression of the second response was significantly heightened when the membrane potential was depolarized from −70 to +50 mV. 5 The degree of desensitization produced was closely linked to receptor occupancy. The rate of current deactivation was also voltage dependent when non‐saturating, and therefore less desensitizing, applications of GABA were analysed. In contrast, both the GABA EC 50 (≈30 μM) and the current activation kinetics at near EC 50 agonist concentrations appeared to be voltage independent.