Proteins within the intracellular calcium store determine cardiac RyR channel activity and cardiac output

Angela F. Dulhunty, Elize Wium, Amy Hanna, Shamaruh Mirza, Sadik Talukder, Nuur Ghazali, Nicole BEARD

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

1. 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).
2. 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.
3. 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.
4. 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
Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology (Online)
Volume39
Issue number5
DOIs
Publication statusPublished - 2012

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