Myosin light chain kinase controls voltage-dependent calcium channels in vascular smooth muscle

Martinsen, Anneloes, Schakman, Olivier, Yerna, Xavier, Dessy, Chantal and Morel, Nicole (2014) Myosin light chain kinase controls voltage-dependent calcium channels in vascular smooth muscle. Pflugers Archive, 466 (7). pp. 1377-1389.

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Abstract

The Ca(2+)-dependent kinase myosin light chain kinase (MLCK) is the activator of smooth muscle contraction. In addition, it has been reported to be involved in Ca(2+) channel regulation in cultured cells, and we previously showed that the MLCK inhibitor ML-7 decreases arginine vasopressin (AVP)-induced Ca(2+) influx in rat aorta. This study was designed to investigate whether MLCK is involved in Ca(2+) regulation in resistance artery smooth muscle cell, which plays a major role in the control of blood pressure. As ML compounds were shown to have off-target effects, MLCK was downregulated by transfection with a small interfering RNA targeting MLCK (MLCK-siRNA) in rat small resistance mesenteric artery (RMA) and in the rat embryonic aortic cell line A7r5. Noradrenaline-induced contraction and Ca(2+) signal were significantly depressed in MLCK-siRNA compared to scramble-siRNA-transfected RMA. Contraction and Ca(2+) signal induced by high KCl and voltage-activated Ca(2+) current were also significantly decreased in MLCK-siRNA-transfected RMA, suggesting that MLCK depletion modifies voltage-operated Ca(2+) channels. KCl- and AVP-induced Ca(2+) signals and voltage-activated Ca(2+) current were decreased in MLCK-depleted A7r5 cells. Eventually, real-time quantitative PCR analysis indicated that in A7r5, MLCK controlled mRNA expression of CaV1.2 (L-type) and CaV3.1 (T-type) voltage-dependent Ca(2+) channels. Our results suggest that MLCK controls the transcription of voltage-dependent Ca(2+) channels in vascular smooth muscle cells.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/24162...
Depositing User:	Pure Connector
Date Deposited:	18 Sep 2015 13:50
Last Modified:	21 Oct 2022 23:47
URI:	https://ueaeprints.uea.ac.uk/id/eprint/54346
DOI:	10.1007/s00424-013-1380-3

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