Expression and function of inwardly rectifying potassium channels after experimental subarachnoid hemorrhage

Cerebral vasospasm after subarachnoid hemorrhage (SAH) is because of smooth muscle contraction, although the mechanism of this contraction remains unresolved. Membrane potential controls the contractile state of arterial myocytes by gating voltage-sensitive calcium channels and is in turn primarily controlled by K(+) ion conductance through several classes of K(+) channels. We characterized the role of inwardly rectifying K(+) (K(IR)) channels in vasospasm. Vasospasm was created in dogs using the double-hemorrhage model of SAH. Electrophysiological, real-time quantitative reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemistry, and isometric tension techniques were used to characterize the expression and function of K(IR) channels in normal and vasospastic basilar artery 7 days after SAH. Subarachnoid hemorrhage resulted in severe vasospasm of the basilar artery (mean of 61% +/- 5% reduction in diameter). Membrane potential of pressurized vasospastic basilar arteries was significantly depolarized compared with control arteries (-46 +/- 1.4 mV versus -29.8 +/- 1.8 mV, respectively, P < 0.01). In whole-cell patch clamp of enzymatically isolated basilar artery myocytes, average K(IR) conductance was 1.6 +/- 0.5 pS/pF in control cells and 9.2 +/- 2.2 pS/pF in SAH cells (P = 0.007). Blocking K(IR) channels with BaCl(2) (0.1 mmol/L) resulted in significantly greater membrane depolarization in vasospastic compared with normal myocytes. Expression of K(IR) 2.1 messenger ribonucleic acid (mRNA) was increased after SAH. Western blotting and immunohistochemistry also showed increased expression of K(IR) protein in vasospastic smooth muscle. Blockage of K(IR) channels in arteries under isometric tension produced a greater contraction in SAH than in control arteries. These results document increased expression of K(IR) 2.1 mRNA and protein during vasospasm after experimental SAH and suggest that this increase is a functionally significant adaptive response acting to reduce vasospasm.