De nouveaux partenaires dans l'intimité du couple canal calcique de type L-récepteur de la ryanodine dans le muscle cardiaque.

Abstract

Comment l' activite electrique controle l' ouverture des recepteurs de la ryanodine? Telle est la principale question posee par le couplage excitation-contraction des myocytes cardiaques et squelettiques depuis plus d' une vingtaine d' annees. Les travaux menes ces dernieres annees sur le couplage excitation-contraction ont parfaitement etabli l' existence d' un controle local de la contraction du muscle cardiaque. Ils ont egalement montre que ce controle local met en jeu de nombreuses proteines associees au complexe canaux calciquesrecepteurs de la ryanodine. Ces proteines permettent non seulement les interactions proteine-proteine mais reglent egalement plus ou moins directement l' activite des recepteurs de la ryanodine. Ces donnees soulignent l' importance de l' observation, au cours des cardiopathies, de modifications du couplage fonctionnel entre les canaux calciques et les recepteurs de la ryanodine, qui pourraient intervenir precocement dans les alterations du couplage excitation-contraction.

The central question of the excitation-contraction coupling process over the past two decades has been how the L-type Ca2+ channel controls the gating of the ryanodine receptor in cardiac and skeletal muscle. In cardiac myocytes, the general scheme that has emerged provides a primary role for transmembrane influx of Ca2+ through the L-type Ca2+ channels in the gating of ryanodine receptors. However, the difficulty to reproduce the excitation-contraction coupling process in non-muscle cells expressing both L-type Ca2+ channels and ryanodine receptor has strongly suggested that the gating of intracellular Ca2+ stores release required actors other than the two Ca2+ channels. Indeed, a number of biochemical and molecular studies have identified likely candidates for such a partnership with the L-type Ca2+ channel-ryanodine receptor complex. Although only limited information is yet available on the exact function of these proteins in the excitation-contraction coupling process, it already seems clear that they play a major role not only in the physiology of cardiac and skeletal muscle but also in their pathophysiology.