TRPV4-Like Non-selective Cation Currents in Cultured Aortic Myocytes

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In this study, we provide evidence of critical changes in the expression of non-selective cation currents (NSCC) during culture in rat aortic myocytes. A selective TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4αPDD), had little effect on membrane currents and intracellular Ca2+ (Ca2+i) in freshly isolated cells from the aorta. In contrast, in cultured aortic myocytes with and without serum, 4αPDD at a concentration range between 0.3 and 3 μM effectively elevated Ca2+i, which was abolished in the absence of external Ca2+. Application of 4αPDD to cultured aortic myocytes also activated NSCC, which had a reversal potential of +3 mV. Both of these signals were blocked by ruthenium red (RuR), an effective blocker of TRPVs. Although the expression of TRPV4 mRNA transcript was found in cultured as well as non-cultured aortic myocytes, significant immunoreactivity to TRPV4 protein was only detected in cultured rat aortic myocytes. Moreover, cultured human pulmonary arterial smooth muscle cells (hPASM) had a substantial response to 4αPDD, which was susceptible to the removal of external Ca2+ and application of RuR. These results provide a strong basis for our proposal that endogenous TRPV4 functions as an important regulator of Ca2+i in vascular myocytes under some physiological and pathophysiological conditions.
社団法人日本薬理学会の論文
2008-10-20