Amplification of EDHF‐type vasodilatations in TRPC1‐deficient mice

摘要: BACKGROUND AND PURPOSE TRPC1 channels are expressed in the vasculature and putative candidates for intracellular Ca2+ handling. However, little is known about their role endothelium-dependent vasodilatations including endothelium-derived hyperpolarizing factor (EDHF) vasodilatations, which require activation of Ca2+-activated K+ (KCa). To provide molecular information on KCa function EDHF signalling complex, we examined independent currents smooth muscle contractility TRPC1-deficient mice (TRPC1-/-). EXPERIMENTAL APPROACH Vascular responses were studied using pressure/wire myography intravital microscopy. We performed electrophysiological measurements, confocal imaging studying channel functions sparks. KEY RESULTS deficiency carotid arteries produced a twofold augmentation TRAM-34- UCL1684-sensitive EDHF-type endothelial hyperpolarization to acetylcholine. NO-mediated unchanged. TRPC1-/- exhibited enhanced resistance-sized arterioles vivo associated with reduced spontaneous tone. Endothelial IKCa/SKCa-type currents, cell sparks BKCa-mediated transient outward unchanged TRPC1-/-. Smooth induced by receptor-operated influx or release endothelium-independent unaltered lower systolic blood pressure as determined tail-cuff measurements. CONCLUSIONS IMPLICATIONS Our data demonstrate that acts negative regulator channel-dependent thereby contributes regulation. Thus, propose specific EDHF–KCa complex suggest pharmacological inhibition TRPC1, enhancing may be novel strategy lowering pressure.