In:
Cell Proliferation, Wiley, Vol. 56, No. 4 ( 2023-04)
Abstract:
The increased proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of vascular diseases. The intermediate conductance calcium‐activated potassium (IK Ca ) channel plays a critical role in VSMC proliferation by raising the intracellular calcium concentration ([Ca 2+ ] i ), but the underlying mechanism is still not unclear. Here we investigated the cooperation between IK Ca and transient receptor potential canonical 1 (TRPC1) channels in mediating extracellular Ca 2+ entry, which in turn activates downstream Ca 2+ signalling in the regulation of VSMC proliferation using serum‐induced cell proliferation model. Serum‐induced cell proliferation was accompanied with up‐regulation of IK Ca expression and an increase in [Ca 2+ ] i . Serum‐induced cell proliferation and increase in [Ca 2+ ] i were suppressed by IK Ca inhibition with TRAM‐34 or IK Ca knockdown. Serum‐induced cell proliferation was strongly reduced by the removal of extracellular Ca 2+ with EGTA or intracellular Ca 2+ with BAPTA‐AM and, additionally, by TRPC1 knockdown. Moreover, the increase in [Ca 2+ ] i induced by serum or by IK Ca 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 Ca and TRPC1 channels cooperate in mediating Ca 2+ influx that activates the ERK1/2 pathway to promote cell proliferation, thus providing new mechanistic insights into VSMC proliferation.
Type of Medium:
Online Resource
ISSN:
0960-7722
,
1365-2184
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2019986-7
SSG:
12
