Channelpedia

PubMed 26202353


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC6



Title: Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation via TRPC6 Channels in Cultured Human Mesangial Cells.

Authors: Fanwu Kong, Linlin Ma, Li Zou, Kexin Meng, Tianrong Ji, Lei Zhang, Rui Zhang, Jundong Jiao

Journal, date & volume: Cell. Physiol. Biochem., 2015 , 36, 1928-38

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26202353


Abstract
There is accumulating evidence that sympathetic nervous hyperactivity contributes to the pathogenesis of glomerular sclerosis independent of blood pressure effects. A previous study showed that α1-adrenoceptor (α1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the underlying mechanism remains unclear.We found that α1-AR is expressed in a human mesangial cell line. The α1-AR agonist phenylephrine (PE) induced Ca(2+) influx as well as release from intracellular Ca(2+) stores. Blockade of TRPC6 with siRNA, anti-TRPC6 antibodies and a TRPC blocker attenuated the PE-induced [Ca(2+)]i increase. Additionally, the PE-induced [Ca(2+)]i increase was phospholipase C dependent. Furthermore, PE induced a [Ca(2+)]i increase even when the intracellular Ca(2+) stores were already depleted. This effect was mimicked by an analog of diacylglycerol. These results suggested that, upon α1-AR stimulation, TRPC6 mediates Ca(2+) influx via a receptor-operated Ca(2+) entry mechanism. Finally, TRPC6 contributes to the PE-induced MC proliferation. The mechanisms are associated with the extracellular signal-regulated kinase (ERK) signaling pathway because blockade of TRPC6 and chelation of extracellular Ca(2+) abrogated PE-induced ERK1/2 abrogated PE-induced ERK1/2 phosphorylation.TRPC6 channels are involved in α1-AR activation-induced Ca(2+) entry, which mediates proliferation via ERK signaling in human MCs.