GABA(B) receptor-activated inwardly rectifying potassium current in dissociated hippocampal CA3 neurons

GABA and the GABA(B) receptor agonist baclofen activated a potassium conductance in acutely dissociated hippocampal CA3 neurons. Baclofen-activated current required internal GTP, was purely potassium selective, and showed strong inward rectification. As with acetylcholine-activated current in atrial myocytes, external Cs- blocked inward but not outward current in a highly voltage-dependent manner, whereas Ba2+ blocked with no voltage dependence. Unlike the cardiac rent, however, the baclofen-activated current showed no intrinsic voltage-dependent relaxation. With fast solution exchange, current was activated by baclofen or GABA with a lag of similar to 50 msec followed by an exponential phase (time constant similar to 225 msec al saturating agonist concentrations); deactivation was preceded by a lag of similar to 50 msec and occurred with a time constant of similar to 1 sec. GABA activated the potassium conductance with a half maximally effective concentration (EC(50)) of 1.6 mu M, much lower than that for activation of GABA(A) receptor-activated chloride current in the same cells (EC(50) similar to 25 mu M) At low GABA concentrations, activation of the GABA(B) current had a Hill coefficient of 1.4-2.1, suggesting cooperativity in the receptor-io-channel pathway. Although the maximal conductance activated by GABA(B) receptors is much smaller than that activated by GABA(A) receptors, its higher sensitivity to GABA and slower time course make it well suited to respond to low concentrations of extra-synaptic GABA.