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J Physiol Volume 584, Number 1, 205-219, October 1, 2007 DOI: 10.1113/jphysiol.2007.138982
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CARDIOVASCULAR

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

Kirill Essin1,2, Andrea Welling3, Franz Hofmann3, Friedrich C. Luft2, Maik Gollasch1,2 and Sven Moosmang3

1 Department of Nephrology and Medical Intensive Care, Charité Campus Virchow-Klinikum, Berlin, Germany
2 Franz Volhard Clinic, HELIOS Klinikum Berlin, Charité Campus Berlin-Buch, and Max Delbrück Center for Molecular Medicine, Berlin, Germany
3 Department of Pharmacology and Toxicology, Technical University München, Munich, Germany

In arterial vascular smooth muscle cells (VSMCs), 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 VSMCs 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 VSMCs weakly reflected the voltage dependency of L-type channels. This study provides evidence that local and tight coupling between the Cav1.2 channels and ryanodine receptors (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.

(Received 19 June 2007; accepted after revision 27 July 2007; first published online 2 August 2007)
Corresponding author M. Gollasch: Charité Campus Virchow Klinikum, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. Email: maik.gollasch{at}charite.de


This paper has online supplemental material.


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