Mechanisms and Models of Cardiac Excitation-Contraction Coupling

Abstract

Intracellular calcium (Ca²⁺) concentration plays an important regulatory role in a number of cellular processes. Cellular influx of Ca²⁺ activates intracellular signaling pathways that in turn regulate gene expression. Studies have identified over 300 genes and 30 transcription factors which are regulated by intracellular Ca²⁺ [1,2]. Fluctuation of intracellular Ca²⁺ levels is also known to regulate intracellular metabolism by activation of mitochondrial matrix dehydrogenases. The subsequent effects on the tri-carboxylic acid cycle increase the supply of reducing equivalents (NADH, FADH2), stimulating increased flux of electrons through the respiratory chain [3]. Most importantly, Ca²⁺ is a key signaling molecule in excitation-contraction (EC) coupling, the process by which electrical activation of the cell is coupled to mechanical contraction and force generation.