Channelpedia

PubMed 21998324


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav1.2



Title: Splice variant specific modulation of CaV1.2 calcium channel by galectin-1 regulates arterial constriction.

Authors: Juejin Wang, Sharon S C Thio, Sophia S H Yang, Dejie Yu, Chye Yun Yu, Yuk Peng Wong, Ping Liao, Shengnan Li, Tuck Wah Soong

Journal, date & volume: Circ. Res., 2011 Nov 11 , 109, 1250-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21998324


Abstract
Ca(V)1.2 channels are essential for excitation-contraction coupling in the cardiovascular system, and alternative splicing optimizes its role. Galectin-1 (Gal-1) has been reported to regulate vascular smooth muscle cell (VSMC) function and play a role in pulmonary hypertension. We have identified Gal-1 multiple times in yeast 2-hybrid assays using the Ca(V)1.2 I-II loop as bait.Our hypothesis is that Gal-1 interacts directly with Ca(V)1.2 channel at the I-II loop to affect arterial constriction.Unexpectedly, Gal-1 was found to selectively bind to the I-II loop only in the absence of alternatively spliced exon 9*. We found that the current densities of Ca(V)1.2(Δ9*) channels were significantly inhibited as a result of decreased functional surface expression due to the binding of Gal-1 at the export signal located on the C-terminus of exon 9. Moreover, the suppression of Gal-1 expression by siRNA in rat A7r5 and isolated VSMCs produced the opposite effect of increased I(Ca,L). The physiological significance of Gal-1 mediated splice variant-specific inhibition of Ca(V)1.2 channels was demonstrated in organ bath culture where rat MAs were reversibly permeabilized with Gal-1 siRNA and the arterial wall exhibited increased K(+)-induced constriction.The above data indicated that Gal-1 regulates I(Ca,L) via decreasing the functional surface expression of Ca(V)1.2 channels in a splice variant selective manner and such a mechanism may play a role in modulating vascular constriction.