Calcium-independent GABA release from striatal slices: the role of calcium channels.
We have investigated the role of Ca2+ and Ca2+ channels in the modulation of GABA release. Brain slices prepared from rat striatum were preincubated with [3H]GABA, superfused with Krebs bicarbonate buffer, and exposed to electrical field stimulation (2 Hz for 3 min). Tritium efflux was measured as an index of GABA release. Both resting and evoked efflux were greatly accelerated by deleting Ca2+ from the medium and adding EGTA (1 mM). However, when the concentration of Mg2+ in the buffer was elevated to 10 mM, no effect of the Ca2(+)-deficiency was observed on resting release and its impact on evoked overflow was diminished. Moreover, addition of verapamil (10 microM), a Ca2+ channel blocking agent, reduced evoked overflow even in the absence of external Ca2+, while 4-aminopyridine (10 microM), a K+ channel inhibitor, enhanced GABA efflux in normal buffer but had no effect in the absence of Ca2+. Finally, we have shown previously that nipecotic acid, an inhibitor of high affinity GABA transport, increases GABA overflow in normal buffer, but blocks it in Ca2(+)-free buffer. Collectively, these results suggest that Ca2+ channels may play two roles in the regulation of depolarization-induced GABA release. Firstly, these channels permit a depolarization-induced influx of Ca2+ which then promotes GABA release. In addition, these channels influence GABA release through a mechanism that does not involve external Ca2+. Although the precise nature of this latter involvement is unclear, we propose that the Ca2+ channels serve to permit an influx of Na+, which in turn promotes Ca2(+)-independent release through an influence on the high affinity GABA transport system.
Bernath
S
S
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Zigmond
M J
MJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000172:deficiency / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D015220:Calcium Channels; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D014700:Verapamil; D008274:Magnesium; D011188:Potassium; D002118:Calcium