Decreased frequency of transient outward BK currents in cerebral myocytes following subarachnoid hemorrhage

Abstract

Cerebral vasospasm is a prolonged vasoconstriction causing substantial morbidity and mortality in patients following aneurysmal and subarachnoid hemorrhage (SAH). The mechanisms underlying this pathology remain unclear, but may involve decreased K+ channel activity in cerebral artery myocytes. Ca2+ sparks are localized intracellular Ca2+ release events leading to the transient activation of large conductance Ca2+‐activated K+ (BK) channels. Here, we evaluated transient BK currents in freshly isolated cerebral artery myocytes obtained from a rabbit model of SAH. Transient whole cell BK currents and single channel BK properties were examined using the perforated whole cell and single channel patch‐clamp technique, respectively. We also examined BK channel α and β1 subunit expression using RT‐PCR. Transient BK current frequency was decreased in cerebral artery myocytes from SAH rabbits, however BK channel properties (voltage‐ and Ca2+‐dependence) and expression were unchanged. These data suggest decreased Ca2+ spark frequency or an uncoupling between Ca2+ spark and BK channel activation may underlie the observed decrease in transient BK frequency. A reduction in BK channel activity in cerebral artery myocytes may contribute to cerebral vasospasm following SAH. This work was supported by the Totman Medical Research Trust, the Peter Martin Brain Aneurysm Endowment, the AHA and the NIH.