Genetic Ablation of CaV3.2 Channels Enhances the Arterial Myogenic Response by Modulating the RyR-BKCa Axis. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Harraz, Osama F.; Brett, Suzanne E.; Zechariah, Anil; Romero, Monica; Puglisi, Jose L.; Wilson, Sean M.; Welsh, Donald G.
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 8(2015)
• Publication Date: 2015-08
• Subjects: arteries -- calcium-activated potassium channels -- calcium channels -- calcium signaling -- ryanodine receptors -- T-type calcium channels -- vascular smooth muscle; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305736
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: In resistance arteries, there is an emerging view that smooth muscle CaV 3.2 channels restrain arterial constriction through a feedback response involving the large-conductance Ca 2+ -activated K + channel (BKCa ). Here, we used wild-type and CaV 3.2 knockout (CaV 3.2 −/− ) mice to definitively test whether CaV 3.2 moderates myogenic tone in mesenteric arteries via the CaV 3.2-ryanodine receptor-BKCa axis and whether this regulatory mechanism influences blood pressure regulation. Approach and Results—: Using pressurized vessel myography, CaV 3.2 −/− 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 CaV 3.2 blocker, to either constrict arteries or suppress T-type currents in CaV 3.2 −/− 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 CaV 3.2 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 CaV 3.2 channel moderated myogenic constriction of resistance arteries, the blood pressure measurements of CaV 3.2 −/− and wild-type animals were similar. Conclusions—: Overall, our findings establish a negative feedback mechanism of the myogenic response in which CaV 3.2 channel modulates downstream ryanodine receptor-BKCa to hyperpolarize and relax arteries. Abstract : Supplemental Digital Content is available in the text.