Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output
Date
2012
Authors
Dulhunty, Angela
Wium, Elize
Li, Linwei
Hanna, Amy
Mirza, Shamaruh
Talukder, Sadik
Ghazali, Nuur
Beard, Nicole
Journal Title
Journal ISSN
Volume Title
Publisher
Blackwell Science Asia
Abstract
The contractile function of the heart requires the release of Ca2+ from intracellular Ca2+ stores in the sarcoplasmic reticulum (SR) of cardiac muscle cells. The efficacy of Ca2+ release depends on the amount of Ca2+ loaded into the Ca2+ store and the way in which this 'Ca2+ load' influences the activity of the cardiac ryanodine receptor Ca2+ release channel (RyR2). The effects of the Ca2+ load on Ca2+ release through RyR2 are facilitated by: (i) the sensitivity of RyR2 itself to luminal Ca2+ concentrations; and (ii) interactions between the cardiac Ca2+-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 Ca2+. 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.
Description
Keywords
Keywords: calcium ion; calsequestrin; junctin; protein; ryanodine receptor 2; sarcoplasmic reticulum calcium transporting adenosine triphosphatase; triadin; unclassified drug; article; binding affinity; binding site; calcium cell level; calcium transport; catechola Calcium signalling; Calsequestrin; Cardiac muscle; Junctin; Luminal calcium dependence of calcium release; Protein-protein interactions; Ryanodine receptor calcium release channel; Sarcoplasmic reticulum; Triadin
Citation
Collections
Source
Clinical and Experimental Pharmacology and Physiology
Type
Journal article
Book Title
Entity type
Access Statement
License Rights
Restricted until
2037-12-31
Downloads
File
Description