Erythrocyte lysate releases Ca2+ from IP3-sensitive stores and activates Ca(2+)-dependent K+ channels in rat basilar smooth muscle cells.

ABSTRACT

Erythrocyte lysate increases intracellular Ca2+ ([Ca2+]i), contracts cerebral arteries and has been suggested to be the causative agent for cerebral vasospasm. However, the mechanism of erythrocyte lysate-induced [Ca2+]i mobilization is not clear. This study was undertaken to investigate the action of erythrocyte lysate on [Ca2+]i mobilization by monitoring [Ca2+]i and the Ca(2+)-dependent K+ channels (KCa) in freshly isolated rat basilar artery smooth muscle cells. In a [Ca2+]i imaging study, erythrocyte lysate produced a biphasic response, a transient peak and a prolonged plateau [Ca2+]i elevation. In the absence of external Ca2+, erythrocyte lysate induced only a transient peak [Ca2+]i response without a marked plateau phase, indicating the [Ca2+]i was Ca2+ released from internal stores. Erythrocyte lysate-induced plateau [Ca2+]i response was resistant to nicardipine, a voltage-dependent Ca2+ channel blocker, but was abolished by EGTA. Elevation of [Ca2+]i induced by erythrocyte lysate contracted smooth muscle cells. In the electrophysiological study, elevation of [Ca2+]i by erythrocyte lysate increased KCa currents in whole-cell patch-clamp configuration. This effect of erythrocyte lysate on KCa was blocked by heparin, an antagonist of IP3 receptors. We conclude that erythrocyte lysate releases Ca2+ from IP3-sensitive intracellular stores and produces Ca2+ entry from voltage-independent Ca2+ pathways.