Evidence for a role of KCNQ channels in regulating contractility in rat myometrium

KCNQ genes encode a family of K + channel α‐subunits influencing cellular excitability in neurons and cardiomyocytes. KCNQ1 combined with an auxillary subunit encoded by KCNE1 produces the slow activating component of the cardiac delayed rectifier (IK S ). KCNQ2/KCNQ3 heteromultimers carry the M current. Little is known about their role in smooth muscle. However, KCNQ1 is expressed in murine portal vein (Ohya et al 2003) where it contributes to the resting membrane conductance (Yeung & Greenwood 2005). The potential role of KCNQ channels in regulating basal spontaneous contractions in non‐pregnant rat myometrium was assessed using antagonists of these channels. Activity was measured as mean integral tension (MIT). MIT after drug application was expressed as a percentage of that during the preceding 15 min control period. Linopirdine, which inhibits the KCNQ2/KCNQ3 heteromultimer, increased MIT by 184 ± 34% at a concentration of 10 μM (n=4; P<0.01). Its more potent analogue XE991 caused a concentration‐dependent increase in MIT, with the greatest increase at 10 μM (mean increase 201 ± 32% n=8; P<0.01). Chromanol 293B, which inhibits the IK S channel, did not affect MIT (85 ± 11% n=4; ns). These results suggest that KCNQ2/KCNQ3 heteromultimers but not IK S may be involved in regulating basal myometrial contractility.