Indirect coupling between Cav1.2 channels and RyR to generate Ca2+ sparks in murine arterial smooth muscle cells

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Item Type:	Article
Title:	Indirect coupling between Cav1.2 channels and RyR to generate Ca2+ sparks in murine arterial smooth muscle cells
Creators Name:	Essin, K., Welling, A., Hofmann, F., Luft, F.C., Gollasch, M. and Moosmang, S.
Abstract:	In arterial vascular smooth muscle cells (VSMC), Ca2+ sparks stimulate nearby Ca2+-activated K+ (BK) channels that hyperpolarize the membrane and close L-type Ca2+ channels. We tested the contribution of L-type Cav1.2 channels to Ca2+ spark regulation in tibial and cerebral artery VSMC using VSMC-specific Cav1.2 channel gene disruption in (SMAKO) mice and an approach based on Poisson statistical analysis of activation frequency and first latency of elementary events. Cav1.2 channel gene inactivation reduced Ca2+ spark frequency and amplitude by ~50% and ~80%, respectively. These effects were associated with lower global cytosolic Ca2+ levels and reduced sarcoplasmic reticulum (SR) Ca2+ load. Elevating cytosolic Ca2+ levels reversed the effects completely. The activation frequency and first latency of elementary events in both wild-type and SMAKO VSMC cells weakly reflected the voltage dependency of L-type channels. This study provides evidence that local and tight coupling between the Cav1.2 channels and RyRs is not required to initiate Ca2+ sparks. Instead, Cav1.2 channels contribute to global cytosolic [Ca2+], which in turn influences luminal SR calcium and thus Ca2+ sparks.
Keywords:	Basilar Artery, Calcium, Cultured Cells, Cytosol, Dihydropyridines, L-Type Calcium Channels, Ryanodine Receptor Calcium Release Channel, Sarcoplasmic Reticulum, Smooth Muscle Myocytes, Tibial Arteries, Vascular Smooth Muscle, Animals, Mice
Source:	Journal of Physiology
ISSN:	0022-3751
Publisher:	Blackwell Publishing
Volume:	584
Number:	Pt. 1
Page Range:	205-219
Date:	1 October 2007
Official Publication:	https://doi.org/10.1113/jphysiol.2007.138982
PubMed:	View item in PubMed

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