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BioMed Research International
Volume 2013, Article ID 390493, 10 pages
Research Article

Dantrolene-Induced Inhibition of Skeletal L-Type Ca2+ Current Requires RyR1 Expression

Division of Cardiology, Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, P-15 8006, B-139, Aurora, CO 80045, USA

Received 20 April 2012; Revised 6 June 2012; Accepted 6 June 2012

Academic Editor: Dobromir Dobrev

Copyright © 2013 R. A. Bannister. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Malignant hyperthermia (MH) is a pharmacogenetic disorder most often linked to mutations in the type 1 ryanodine receptor (RyR1) or the skeletal L-type Ca2+ channel (CaV1.1). The only effective treatment for an MH crisis is administration of the hydantoin derivative Dantrolene. In addition to reducing voltage induced Ca2+ release from the sarcoplasmic reticulum, Dantrolene was recently found to inhibit L-type currents in developing myotubes by shifting the voltage-dependence of CaV1.1 channel activation to more depolarizing potentials. Thus, the purpose of this study was to obtain information regarding the mechanism of Dantrolene-induced inhibition of CaV1.1. A mechanism involving a general depression of plasma membrane excitability was excluded because the biophysical properties of skeletal muscle Na+ current in normal mouse myotubes were largely unaffected by exposure to Dantrolene. However, a role for RyR1 was evident as Dantrolene failed to alter the amplitude, voltage dependence and inactivation kinetics of L-type currents recorded from dyspedic (RyR1 null) myotubes. Taken together, these results suggest that the mechanism of Dantrolene-induced inhibition of the skeletal muscle L-type Ca2+ current is related to altered communication between CaV1.1 and RyR1.