Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output
Language: 
English
Abstract: 

SUMMARY: The contractile function of the heart requires the release of Ca(2+) from intracellular Ca(2+) stores in the sarcoplasmic reticulum (SR) of cardiac muscle cells. The efficacy of Ca(2+) release depends on the amount of Ca(2+) loaded into the Ca(2+) store and the way in which this 'Ca(2+) load' influences the activity of the cardiac ryanodine receptor Ca(2+) release channel (RyR2). The effects of the Ca(2+) load on Ca(2+) release through RyR2 are facilitated by: (i) the sensitivity of RyR2 itself to luminal Ca(2+) concentrations; and (ii) interactions between the cardiac Ca(2+) -binding protein calsequestrin (CSQ) 2 and RyR2, transmitted through the 'anchoring' proteins junctin and/or triadin. Mutations in RyR2 are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death. The tachycardia is associated with changes in the sensitivity of RyR2 to luminal Ca(2+) . Triadin-, junctin- or CSQ-null animals survive, but their longevity and ability to tolerate stress is compromised. These studies reveal the importance of the proteins in normal muscle function, but do not reveal the molecular nature of their functional interactions, which must be defined before changes in the proteins leading to CPVT and heart disease can be understood. Herein, we discuss known interactions between the RyR, triadin, junctin and CSQ with emphasis on the cardiac isoforms of the proteins. Where there is little known about the cardiac isoforms, we discuss evidence from skeletal isoforms.

Author(s): 
Dulhunty, Angela F.
Wium, Elize
Li, Linwei
Hanna, Amy D.
Mirza, Shamaruh
Talukder, Sadik
Ghazali, Nuur Aa
Beard, Nicole A.
Item Type: 
Journal Article
Publication Title: 
Clinical and Experimental Pharmacology & Physiology
Journal Abbreviation: 
Clin. Exp. Pharmacol. Physiol.
Publication Date: 
2012-05
Publication Year: 
2012
Pages: 
477-484
Volume: 
39
Issue: 
5
ISSN: 
1440-1681
DOI: 
10.1111/j.1440-1681.2012.05704.x
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22524859

Turabian/Chicago Citation

Angela F. Dulhunty, Elize Wium, Linwei Li, Amy D. Hanna, Shamaruh Mirza, Sadik Talukder, Nuur Aa Ghazali and Nicole A. Beard. 2012-05. "Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output." Clinical and Experimental Pharmacology & Physiology 39: 5: 477-484. 10.1111/j.1440-1681.2012.05704.x.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1111/j.1440-1681.2012.05704.x | issn = 1440-1681 | volume = 39 | pages = 477-484 | last = Dulhunty | first = Angela F. | coauthors = Wium, Elize, Li, Linwei, Hanna, Amy D., Mirza, Shamaruh, Talukder, Sadik, Ghazali, Nuur Aa, Beard, Nicole A. | title = Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output | journal = Clinical and Experimental Pharmacology & Physiology | date = 2012-05 | pmid = | pmc = }} </ref>