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 real-time 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 Kv 2.2 (65% reduction in mRNA, P < 0.001; 49% reduction in protein, P < 0.05) and the β1 subunit of the large-conductance, Ca2+-activated K+ (BK) channel (53% reduction in mRNA, P < 0.02). There was no change in BK β1 subunit protein. Changes in mRNA levels of Kv 2.2 and the BK-β1 subunit correlated with the degree of vasospasm (r2 = 0.490 and 0.529 respectively, P < 0.05). The inwardly rectifying K+ (Kir) channel Kir 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-α subunit. These data suggest that K+ channel dysfunction may contribute to the pathogenesis of cerebral vasospasm.