Increased myofilament Ca2+-sensitivity and arrhythmia susceptibility.
Increased myofilament Ca(2+) sensitivity is a common attribute of many inherited and acquired cardiomyopathies that are associated with cardiac arrhythmias. Accumulating evidence supports the concept that increased myofilament Ca(2+) sensitivity is an independent risk factor for arrhythmias. This review describes and discusses potential underlying molecular and cellular mechanisms how myofilament Ca(2+) sensitivity affects cardiac excitation and leads to the generation of arrhythmias. Emphasized are downstream effects of increased myofilament Ca(2+) sensitivity: altered Ca(2+) buffering/handling, impaired energy metabolism and increased mechanical stretch, and how they may contribute to arrhythmogenesis.
Huke
Sabine
S
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232-0575, USA.
Knollmann
Björn C
BC
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004198:Disease Susceptibility / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical
D002118:Calcium