Researchers explain mechanism behind rare muscle disorders

December 13, 2010

Researchers have provided the first thorough mechanistic account of how a genetic defect leads to malignant hypothermia (MH) and central core disease (CCD), rare genetic skeletal muscle disorders. The study appears in the January issue of the Journal of General Physiology (www.jgp.org).

Mutations in the type 1 ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum (SR) activated during skeletal muscle excitation-contraction (EC) coupling, give rise to CCD. One of the most common CCD-causing mutations is Ile4895Thr. Now, Robert Dirksen (University of Rochester) and colleagues have provided a comprehensive analysis of the consequences of this mutation in muscle fibers of adult mice heterozygous for the mutation.

The team addressed several questions concerning how RYR1 function is altered by the Ile4895Thr mutation. Their findings demonstrate, for the first time, that the muscle weakness associated with MH and CCD arises from a dominant-negative effect, a reduction in the magnitude and rate of calcium release by the mutant RYR1 receptors during EC coupling. The reduction in calcium release in turn leads to reduced muscle force generation.
-end-
About The Journal of General Physiology

Founded in 1918, The Journal of General Physiology (JGP) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists. JGP content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jgp.org.

Loy, R.E. 2010. J. Gen. Physiol. doi:10.1085/jgp.201010523

Rockefeller University Press

Related Skeletal Muscle Articles from Brightsurf:

Skeletal muscle development and regeneration mechanisms vary by gender
Researchers at Kumamoto University, Japan generated mice lacking the estrogen receptor beta (ERĪ²) gene, both fiber-specific and muscle stem cell-specific, which resulted in abnormalities in the growth and regeneration of skeletal muscle in female mice.

Different response of mitochondrial respiration in skeletal muscle and adipose tissue to endurance e
In obese individuals, endurance exercise improves fitness and increases the number of mitochondria * and cellular respiration in skeletal muscles.

Skeletal study suggests at least 11 fish species are capable of walking
An international team of scientists has identified at least 11 species of fish suspected to have land-walking abilities.

Targeting deep areas of the skeletal muscles effectively alleviates postoperative pain
To address postoperative muscle pain in patients undergoing abdominal surgery, researchers developed a new method of effective pain control called needle electrical twitch obtaining intramuscular stimulation (NETOIMS).

Research reveals insights into bioprinted skeletal muscle tissue models
SUTD collaborates with NTU to provide in-depth analysis of 3D in vitro biomimetic skeletal muscle tissue models, highlighting the great potential of bioprinting technology.

Surplus antioxidants are pathogenic for hearts and skeletal muscle
Oxidative stress can be pathological. Now researchers report that the other end of the redox spectrum, reductive stress, is also pathological.

UCLA scientists create first roadmap of human skeletal muscle development
An interdisciplinary team of researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA has developed a first-of-its-kind roadmap of how human skeletal muscle develops, including the formation of muscle stem cells.

Bone or cartilage? Presence of fatty acids determines skeletal stem cell development
In the event of a bone fracture, fatty acids in our blood signal to stem cells that they have to develop into bone-forming cells.

Neural cells speed up function in 3D bioprinted skeletal muscle constructs
Wake Forest Institute for Regenerative Medicine scientists improve on 3D bioprinting research by investigating the effects of neural cell integration into bioprinted muscle constructs to accelerate functional muscle regeneration.

Bad to the bone: Specific gut bacterium impairs normal skeletal growth and maturation
Bone mass accrual is regulated by the gut microbiome as well as by diet and exercise.

Read More: Skeletal Muscle News and Skeletal Muscle Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.