Article

Toward a molecular understanding of the structure-function of ryanodine receptor Ca2+ release channels

Cell Biochemistry and Biophysics (impact factor: 3.74). 04/2012; 42(2):197-222. DOI:10.1385/CBB:42:2:197 pp.197-222

ABSTRACT Identification of the genetic basis of human diseases linked to dysfunctional free calcium (Ca2+) signaling has triggered an explosion of interest in the functional characterization of the molecular components regulating
intracellular Ca2+ homeostasis. There is a growing appreciation of the central role of intracellular ryanodine-sensitive Ca2+ release channel (RyR) regulation in skeletal and cardiac muscle pathologies, including malignant hyperthermia, heart failure,
and sudden cardiac death. The use of cloned RyR isoforms and recombinant expression techniques has greatly facilitated the
elucidation of the molecular basis of RyR Ca2+ release functionality. This review will focus on the recombinant techniques used in the functional characterization of recombinant
RyR isoforms and the insights that these approaches have yielded in unraveling the mechanistic basis of RyR channel functionality.

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Keywords

approaches
 
cardiac muscle pathologies
 
central role
 
dysfunctional free calcium
 
elucidation
 
functional characterization
 
genetic basis
 
growing appreciation
 
intracellular ryanodine-sensitive Ca2+ release channel
 
malignant hyperthermia
 
mechanistic basis
 
molecular basis
 
recombinant expression techniques
 
recombinant techniques
 
RyR Ca2+ release functionality
 
RyR channel functionality
 
skeletal
 
sudden cardiac death