Referenced in: none

Automatically associated channels: Cav3.2 , Slo1

Title: Genetic ablation of CaV3.2 channels enhances the arterial myogenic response by modulating the RyR-BKCa axis.

Authors: Osama F Harraz, Suzanne E Brett, Anil Zechariah, Monica Romero, Jose L Puglisi, Sean M Wilson, Donald G Welsh

Journal, date & volume: Arterioscler. Thromb. Vasc. Biol., 2015 Aug , 35, 1843-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26069238

Abstract
In resistance arteries, there is an emerging view that smooth muscle CaV3.2 channels restrain arterial constriction through a feedback response involving the large-conductance Ca(2+)-activated K(+) channel (BKCa). Here, we used wild-type and CaV3.2 knockout (CaV3.2(-/-)) mice to definitively test whether CaV3.2 moderates myogenic tone in mesenteric arteries via the CaV3.2-ryanodine receptor-BKCa axis and whether this regulatory mechanism influences blood pressure regulation.Using pressurized vessel myography, CaV3.2(-/-) mesenteric arteries displayed enhanced myogenic constriction to pressure but similar K(+)-induced vasoconstriction compared with wild-type C57BL/6 arteries. Electrophysiological and myography experiments subsequently confirmed the inability of micromolar Ni(2+), a CaV3.2 blocker, to either constrict arteries or suppress T-type currents in CaV3.2(-/-) smooth muscle cells. The frequency of BKCa-induced spontaneous transient outward K(+) currents dropped in wild-type but not in knockout arterial smooth muscle cells upon the pharmacological suppression of CaV3.2 channel. Line scan analysis performed on en face arteries loaded with Fluo-4 revealed the presence of Ca(2+) sparks in all arteries, with the subsequent application of Ni(2+) only affecting wild-type arteries. Although CaV3.2 channel moderated myogenic constriction of resistance arteries, the blood pressure measurements of CaV3.2(-/-) and wild-type animals were similar.Overall, our findings establish a negative feedback mechanism of the myogenic response in which CaV3.2 channel modulates downstream ryanodine receptor-BKCa to hyperpolarize and relax arteries.