Caveolin‐1 ablation induces functional K Ca channel activation and attenuates the myogenic response in cerebral arteries

Intravascular pressure‐induced vasoconstriction (the “myogenic response”) is intrinsic to arterial myocytes, but mechanisms that underlie this response are unresolved. Here, we investigated the physiological function of caveolin‐1, a protein required for arterial myocyte caveolae formation, in mediating the cerebral artery myogenic response. Pressure‐induced changes in arterial wall membrane potential, intracellular calcium concentration ([Ca 2+ ] i ), and myogenic tone were attenuated in cerebral arteries from cav‐1 deficient (cav‐1 −/− ) mice, when compared with arteries from control (cav‐1 +/+ ) mice. Although 60 mM K + induced a smaller [Ca 2+ ] i elevation and constriction in cav‐1 −/− arteries, extracellular Ca 2+ removal and diltiazem, an L‐type Ca 2+ channel blocker, similarly dilated cav‐1 +/+ and cav‐1 −/− arteries. Iberiotoxin, a selective K Ca channel blocker, induced a similar depolarization and constriction in pressurized cav‐1 +/+ and cav‐1 −/− arteries. However, total K Ca channel protein was similar in cav‐1 +/+ and cav‐1 −/− arteries. Given that the hyperpolarized membrane potential of cav‐1 −/− arteries would reduce K Ca channel current, these data suggest that K Ca channel activity is elevated in cav‐1 −/− arteries and may contribute to the attenuated myogenic constriction. In summary, data indicate that cav‐1 expression is required for a full cerebral artery myogenic response.