GABAB agonists modulate a transient potassium current in cultured mammalian hippocampal neurons.
Depolarization of voltage-clamped cultured rat hippocampal neurons from holding potentials more negative than -60 mV produced a transient outward current with the characteristics of an A-current: it was 50% inactivated at a holding potential of -85 mV and blocked by 4-aminopyridine (1 mM). In the presence of GABA or baclofen (50-200 microM), with or without bicuculline, inactivation of this current was shifted to more positive potentials so that there was little inactivation at -70 mV. Activation of the A-current was also shifted to more positive potentials by these agonists, but the voltage dependence of activation of the sodium current was unaffected. If A-currents with similar properties can influence the time course of action potentials in presynaptic terminals. GABAB agonists could make action potentials briefer by potentiating the A-current and hence depress transmitter release.
Saint
D A
DA
John Curtin School of Medical Research, Australian National University, Canberra, ACT.
Thomas
T
T
Gage
P W
PW
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D015221:Potassium Channels; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D001418:Baclofen