Functional cooperation between IK and TRPC1 channels regulates serum-induced vascular smooth muscle cell proliferation via mediating Ca influx and ERK1/2 activation.

Cell Prolif

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, and with the School of Engineering Medicine, Beihang University, Beijing, China.

Published: April 2023

The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium-activated potassium (IK ) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca ] ), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IK and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca entry, which in turn activates downstream Ca signalling in the regulation of VSMC proliferation using serum-induced cell proliferation model. Serum-induced cell proliferation was accompanied with up-regulation of IK expression and an increase in [Ca ] . Serum-induced cell proliferation and increase in [Ca ] were suppressed by IK inhibition with TRAM-34 or IK knockdown. Serum-induced cell proliferation was strongly reduced by the removal of extracellular Ca with EGTA or intracellular Ca with BAPTA-AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca ] induced by serum or by IK activation with 1-EBIO was attenuated by TRPC1 knockdown. Finally, serum induced ERK1/2 activation, which was attenuated by treatment with TRAM-34 or BAPTA-AM, as well as TRPC1 knockdown. Consistently, serum-induced cell proliferation was suppressed by ERK1/2 inhibition with PD98059. Taken together, these results suggest that the IK and TRPC1 channels cooperate in mediating Ca influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10068941PMC
http://dx.doi.org/10.1111/cpr.13385DOI Listing

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