Dissecting the Role of G-Protein Coupled Receptor Kinase 2 for Excitation-Contraction Coupling
Chronic heart failure is the inability of the left ventricle (LV) to supply the body with sufficient amounts of blood. On the cellular level, this contractile dysfunction is caused by deterioration of excitation-contraction (EC) coupling in cardiac myocytes.1,2 In the normal heart, Ca2+ enters cardiac myocytes via L-type Ca2+ channels (LTCC) and triggers an even greater Ca2+ release from the sarcoplasmic reticulum (SR). This Ca2+ binds to the myofilaments to induce contraction. During diastole, Ca2+ is taken back up into the SR by the SR Ca2+ ATPase (SERCA), and the amount of Ca2+ that entered the cell via LTCC is exported via the Na+/Ca2+-exchanger (NCX). In myocytes of failing hearts, SR Ca2+ load is reduced as a result of decreased SERCA activity and a leak of the Ca2+ release channels in the SR, the ryanodine receptors (RyR). Furthermore, expression and activity of the NCX are elevated in failing myocardium, which further decreases SR Ca2+ load by removing Ca2+ from the cytosol during diastole.2 (SELECT FULL TEXT TO CONTINUE)
- Received March 30, 2012.
- Accepted April 2, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited