GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures.
GABAB receptors are a subclass of receptors for gamma-amino-n-butyric acid (GABA) that are also activated by the antispastic drug beta-p-chlorophenyl-GABA (baclofen). One effect of baclofen is to inhibit excitatory transmission from CA3 to CA1 hippocampal pyramidal cells. To identify the ionic mechanism of GABAB-receptor-mediated depression, we have studied the effect of baclofen and GABA on ionic currents in voltage-clamped CA3 pyramidal cell somata in rat hippocampal slice cultures. Baclofen (10 microM) induced an inwardly rectifying outward current that reversed at -74 +/- 4.3 mV (mean +/- SD). This appeared to be a K+ current since (i) its reversal potential showed the expected shift when extracellular K+ concentration was changed and (ii) it was blocked by external Ba2+ or internal Cs+. The action of baclofen was closely imitated by GABA after the GABAA-mediated Cl- current had been abolished with pitrazepin (10 microM); under these conditions, GABA (100 microM) also produced an inwardly rectifying, Ba2+-sensitive current with a reversal potential identical to that of the baclofen-induced current. When outward currents were blocked with internal Cs+, the residual inward voltage-dependent Ca2+ current was not changed by baclofen. It is concluded that the primary effect of GABAB-receptor activation in these neurones is to increase K+ permeability rather than to reduce Ca2+ permeability.
Gähwiler
B H
BH
Brown
D A
DA
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004553:Electric Conductivity; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D011188:Potassium; D002118:Calcium