Ryanodine receptor and heart disease

Médecine sciences : M/S
Alain LacampagneSylvain Richard

Abstract

Calcium ions (Ca2+) play an essential role in cardiac excitation-contraction coupling. Ca2+ is stored in the sarcoplasmic reticulum (SR) and is release via SR-Ca-release channels (ryanodine receptors, RyR2) to trigger contraction. RyR2 is a homotetramer comprising 4 pore-forming subunits. Each subunit is closely associated to regulatory proteins such as calstabine 2 (FKBP12.6), calmodulin, PKA, CamKII, calsequestrin and form a macromolecular complex that plays a critical role in pathological conditions. As a matter of fact, alterations of the channel activity and/or associated regulatory proteins can cause severe functional alterations resulting in arrhythmias and sudden death. Thus, RyR2 represent a novel therapeutic target and the discovery of a new pharmacological agent able to restore a normal RyR2 channel function represents a major challenge in the cardiac field.

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Citations

Nov 29, 2008·Médecine sciences : M/S·Joël LunardiNicole Monnier
Oct 21, 2015·Médecine sciences : M/S·Yannis Sainte-MarieFrank Lezoualc'h
Mar 9, 2011·Médecine sciences : M/S·Laurent Combettes, Geneviève Dupont

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