Dantrolene-Induced Inhibition of Skeletal L-Type Ca2+ Current Requires RyR1 Expression
Author
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-04
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Bannister, R. A.. 2012. Dantrolene-Induced Inhibition of Skeletal L-Type Ca2+ Current Requires RyR1 Expression. BioMed Research International،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1004178
Modern Language Association (MLA)
Bannister, R. A.. Dantrolene-Induced Inhibition of Skeletal L-Type Ca2+ Current Requires RyR1 Expression. BioMed Research International No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-1004178
American Medical Association (AMA)
Bannister, R. A.. Dantrolene-Induced Inhibition of Skeletal L-Type Ca2+ Current Requires RyR1 Expression. BioMed Research International. 2012. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1004178
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1004178