The inhibition of KCNQ channels as a mechanism for vasopressin‐induced vasoconstriction

KCNQ K + channels play a role in neuronal excitation and are modulated by acetylcholine acting at muscarinic receptors. Although there is no known role for KCNQ channels in vasoconstriction signal transduction we identified an analogous process in vascular smooth muscle. We recently showed that inhibition of KCNQ5 currents in A7r5 cells by vasopressin (AVP) is protein‐kinase C‐dependent and results in membrane depolarization leading to L‐type Ca 2+ channel activation (Brueggemann et al, 2006). We then wanted to evaluate whether Ca 2+ fluxes seen in A7r5 cells translate into a functional role for KCNQ channels in AVP mediated vasoconstriction. Using RT‐PCR, mRNA for KCNQ1 and 2 was detected in rat mesenteric artery smooth muscle cells (MASMCs). Using perforated patch voltage clamp techniques in MASMCs, K + current indicative of KCNQ channels was isolated. KCNQ channel blockers linopirdine and XE‐991 blocked the current whereas the KCNQ channel activator flupirtine enhanced it. The current was also inhibited in response to 100 pM AVP. Using isolated artery pressure myography, we assessed KCNQ involvement in AVP‐mediated vasoconstriction. Constriction induced in 4 th order rat mesenteric arteries by 30 pM AVP did not differ from constriction by 10 μM linopirdine and when combined, the response was not additive. These data suggest that KCNQ channel inhibition contributes to AVP‐mediated vasoconstriction in MASMCs.