GABA induces GABAergic MSCs in cultured embryonic rat thalamic neurons.
Application of 0.1-10 microM GABA in the vicinity of cultured embryonic rat thalamic neurons recorded with patch pipettes in the presence of 2 microM TTX induced or increased the frequency of miniature synaptic currents (MSCs) that reversed polarity at the Cl- equilibrium potential. These MSCs were blocked by the GABAA receptor antagonist bicuculline and exhibited exponential decay kinetics that closely paralleled those estimated from fluctuation analysis of Cl- channels activated pharmacologically by applying 1-10 microM GABA to the same cells. We conclude that the MSCs are mediated by GABA. Application of the GABAA receptor agonist muscimol activated Cl- current but failed to induce GABAergic MSCs while submicromolar concentrations of GABA evoked GABAergic MSCs but did not activate Cl- channels. The GABAB receptor agonist (-)baclofen did not mimic GABA in inducing MSCs. Induction of GABAergic MSCs by GABA required extracellular Ca2+. Verapamil and Co2+, which block voltage-dependent calcium channels, completely blocked GABA-induced MSCs independent of their effects on the direct activation of a Cl- current response. The results indicate that GABA can trigger GABAergic Cl(-)-dependent MSCs in a Cao(2+)-dependent manner. The mechanism may involve a novel receptor and/or signal transduction pathway.
Liu
Q Y
QY
Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Vautrin
J
J
Schaffner
A E
AE
Ma
W
W
Barker
J L
JL
D000818:Animals; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid