Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage

The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6-8 days after SAH. We reported that function of voltage-gated K(+) (K(V)) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K(+) conductance, the compromised K(+) channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K(+) channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K(+) channels (K(V) and large-conductance voltage/Ca(2+)-activated (K(ca)) channels). Electrophysiologic function of K(Ca) channels was preserved at all times after SAH. In contrast, function of K(V) channels was significantly decreased at all times after SAH. The decrease in cell size and degree of K(V) channel dysfunction was maximal 7 days after SAH. The results suggest that K(V) channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before K(V) channels recover their wunction. (C) 2008 Elsevier Ireland Ltd. All rights reserved.