Alterations of single potassium channel activity in CA1 pyramidal neurons after transient forebrain ischemia

Abstract

Selective neuronal injury in the CA1 zone of hippocampus following transient cerebral ischemia has been well documented ( Pulsinelli et al., 1982; Kirino, 1982). Extracellular potassium concentration markedly increases during ischemia/hypoxia ( Hansen, 1985; Schmidt-Kastener and Freund, 1991). Accumulating evidence has indicated that the outward potassium currents, including delayed rectifier potassium current, not only influence membrane excitability but also mediate apoptosis ( Bortner et al., 1997; Hughes et al., 1997; Yu et al., 1997). It has been shown that the amplitude of delayed rectifier potassium current in CA1 neurons significantly increased after cerebral ischemia ( Chi and Xu, 2000b). To elucidate the mechanisms underlying the changes of potassium currents following ischemia, single potassium channel activities of rat CA1 neurons were compared before and after transient forebrain ischemia. Using cell-attached configuration, depolarizing voltage steps activated outward single channel events. The channel properties, the kinetics and pharmacology of these events resemble the delayed rectifier potassium current. After ischemia, the unitary amplitude of single channels significantly increased, the open probability, mean open time and open time constant also significantly increased while the conductance remained unchanged. These data indicate that the increase of single channel activity is responsible, at least in part, for the increase of delayed rectifier potassium current in CA1 neurons after cerebral ischemia.