Molecular profile of vascular ion channels after experimental subarachnoid hemorrhage

Cerebral vasospasm is a transient, delayed constriction of cerebral arteries that occurs after subarachnoid hemorrhage (SAH). Smooth muscle cells show impaired relaxation after SAH, which may be caused by a defect in the ionic mechanisms regulating smooth muscle membrane potential and Ca2+ permeability. We tested this hypothesis by examining changes in expression of mRNA and protein for ion channels in the basilar arteries of dogs after SAH using quantitative realtime polymerase chain reaction (PCR) and western blotting. SAH was associated with a significant reduction in basilar artery diameter to 41 +/- 8% of pre-SAH diameter (P < 0.001) after 7 days. There was significant downregulation of the voltage-gated K+ channel K-v 2.2 (65% reduction in mRNA, P < 0.001; 49% reduction in protein, P < 0.05) and the beta1 subunit of the large-conductance, Ca2+-activated K+ (BK) channel (53% reduction in mRNA, P < 0.02). There was no change in BK beta1 subunit protein. Changes in mRNA levels of Kv 2.2 and the BK-beta1 subunit correlated with the degree of vasospasm (r(2) 0.490 and 0.529 respectively, P < 0.05). The inwardly rectifying K+ (K-ir) channel K-ir 2.1 was upregulated (234% increase in mRNA, P < 0.001; 350% increase in protein, P < 0.001). There was no significant change in mRNA expression of L- type Ca2+ channels and the BK-alpha subunit. These data suggest that K+ channel dysfunction may contribute to the pathogenesis of cerebral vasospasm.