Role of Endogenous ENaC and TRP Channels in the Myogenic Response of Rat Posterior Cerebral Arteries

Abstract

AimsMechanogated ion channels are predicted to mediate pressure-induced myogenic vasoconstriction in small resistance arteries. Recent findings have indicated that transient receptor potential (TRP) channels and epithelial sodium channels (ENaC) are involved in mechanotransduction. The purpose of this study was to investigate the role of TRP channels and ENaC in the myogenic response. Our previous study suggested that ENaC could be a component of the mechanosensitive ion channels in rat posterior cerebral arteries (PCA). However, the specific ion channel proteins mediating myogenic constriction are unknown. Here we found, for the first time, that ENaC interacted with TRPM4 but not with TRPC6 using immunoprecipitation and confocal microscopy.Methods and ResultsTreatment with a specific βENaC inhibitor, amiloride, a specific TRPM4 inhibitor, 9-phenanthrol, and a TRPC6 inhibitor, SKF96365, resulted in inhibition of the pressure-induced myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with small interfering RNA of βENaC, TRPM4, and TRPC6. Co-treatment with amiloride and 9-phenanthrol showed a similar inhibitory effect on myogenic contraction compared to single treatment with amiloride or 9-phenanthrol. The myogenic response was not affected by 9-phenanthrol or amiloride treatment in PCA transfected with βENaC or TRPM4 siRNA, respectively. However, pressure-induced myogenic response was fully inhibited by co-treatment with amiloride, 9-phenanthrol, and SKF96365, and by treatment with SKF96365 in PCA transfected with βENaC siRNA.ConclusionOur results suggest that ENaC, TRPM4, and TRPC6 play important roles in the pressure-induced myogenic response, and that ENaC and TRPM4 interact in rat PCA.

Renal Autoregulation in Health and Disease

“…DEG-like currents in cerebral arterial VSMCs were inhibited by ROS (257). ␤-ENaC in rat posterior cerebral arteries colocalized with TRPM4 but not TRPC6 (793,794), although all three channels participated in myogenic constriction.…”

Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer

“…The muscularis of the bladder is composed of smooth muscle, so one has to consider whether there is precedent for hyperthermia having a direct effect on perfusion of this organ. Activation of TRP (transient receptor potential) channels may be involved in regulating smooth muscle vasodilation upon heat stress [29,30]. Perfusion in tumours can increase as well by as much as 2-fold [27].…”

Involvement of Epithelial Na+ Channel in the Elevated Myogenic Response in Posterior Cerebral Arteries from Spontaneously Hypertensive Rats

“…Recently, several studies reported that the requirement of ENaC proteins for myogenic response7823. In our previous studies, we also showed that the expression of ENaC protein and the effect of ENaC protein blockade with amiloride on myogenic response, and clarified that ENaC protein is critical for the mechanotransduction in the pressure-induced myogenic response1024. However, the ENaC protein has been suggested as mechanotransducer, the involvement of ENaC in the elevated myogenic response in hypertension has not been investigated.…”

“…The PCAs were cannulated with glass micropipettes, and perfused with K-H solution bubbled with a 95% O 2  + 5% CO 2 gas mixture to maintain a pH of 7.4 at 36 °C in an arteriograph system (Living Systems Instrumentation, Burlington, VT, USA) as previously described24. The lumen diameter of PCAs was recorded using the SoftEdge Acquisition Subsystem (IonOptix, Milton, MA, USA).…”