TY - JOUR
T1 - Expression and function of inwardly rectifying potassium channels after experimental subarachnoid hemorrhage
AU - Weyer, George W.
AU - Jahromi, Babak S.
AU - Aihara, Yasuo
AU - Agbaje-Williams, Mayowa
AU - Nikitina, Elena
AU - Zhang, Zhen Du
AU - Macdonald, Robert L.
PY - 2006/3
Y1 - 2006/3
N2 - 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 + (KIR) 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 KIR 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 KIR 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 KIR channels with BaCl2 (0.1 mmol/L) resulted in significantly greater membrane depolarization in vasospastic compared with normal myocytes. Expression of KIR 2.1 messenger ribonucleic acid (mRNA) was increased after SAH. Western blotting and immunohistochemistry also showed increased expression of KIR protein in vasospastic smooth muscle. Blockage of KIR channels in arteries under isometric tension produced a greater contraction in SAH than in control arteries. These results document increased expression of KIR 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.
AB - 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 + (KIR) 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 KIR 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 KIR 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 KIR channels with BaCl2 (0.1 mmol/L) resulted in significantly greater membrane depolarization in vasospastic compared with normal myocytes. Expression of KIR 2.1 messenger ribonucleic acid (mRNA) was increased after SAH. Western blotting and immunohistochemistry also showed increased expression of KIR protein in vasospastic smooth muscle. Blockage of KIR channels in arteries under isometric tension produced a greater contraction in SAH than in control arteries. These results document increased expression of KIR 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.
KW - Cerebral vasospasm
KW - Inward rectifier K channels
KW - Subarachnoid hemorrhage
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U2 - 10.1038/sj.jcbfm.9600193
DO - 10.1038/sj.jcbfm.9600193
M3 - Article
C2 - 16079788
AN - SCOPUS:33644502931
SN - 0271-678X
VL - 26
SP - 382
EP - 391
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -