GABABReceptor-Activated Inwardly Rectifying Potassium Current in Dissociated Hippocampal CA3 Neurons

Abstract

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 Ba 2+blocked with no voltage dependence. Unlike the cardiac current, 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 ∼50 msec followed by an exponential phase (time constant ∼225 msec at saturating agonist concentrations); deactivation was preceded by a lag of ∼150 msec and occurred with a time constant of ∼1 sec. GABA activated the potassium conductance with a half maximally effective concentration (EC 50) of 1.6 μ m, much lower than that for activation of GABA A receptor-activated chloride current in the same cells (EC 50∼25 μ 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-to-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.