Enhancement in activities of large conductance calcium-activated potassium channels in CA1 pyramidal neurons of rat hippocampus after transient forebrain ischemia

It has been reported previously that the neuronal excitability persistently suppresses and the amplitude of fast afterhyperpolarization (fAHP) increases in CA1 pyramidal cells of rat hippocampus following transient forebrain ischemia. To understand the conductance mechanisms underlying these post-ischemic electrophysiological alterations, we compared differences in activities of large conductance Ca2+-activated potassium (BKCa) channels in CA1 pyramidal cells acutely dissociated from hippocampus before and after ischemia by using inside-out configuration of patch clamp techniques. (1) The unitary conductance of BKCa channels in post-ischemic neurons (295 pS) was higher than that in control neurons (245 pS) in symmetrical 140/140 mM K+ in inside-out patch; (2) the membrane depolarization for an e-fold increase in open probability (P-o) showed no significant differences between two groups while the membrane potential required to produce one-half of the maximum P-o was more negative after ischemia, indicating no obvious changes in channel voltage dependence; (3) the [Ca2+](i) required to half activate BKCa channels was only 1 muM in post-ischemic whereas 2 muM in control neurons, indicating an increase in [Ca2+](i) sensitivity after ischemia; and (4) BKCa channels had a longer open time and a shorter closed rime after ischemia without significant differences in open frequency as compared to control. The present results indicate that enhanced activity of BKCa channels in CA1 pyramidal neurons after ischemia may partially contribute to the post-ischemic decrease in neuronal excitability and increase in fAHP. (C) 2000 Elsevier Science B.V. All rights reserved.