Optical bioimaging: from living tissue to a single molecule: atrio-ventricular difference in myocardial excitation-contraction coupling--sequential versus simultaneous activation of SR Ca2+ release units

Abstract

Rapid-scanning cofocal microscopy has been applied to the analysis of early phase Ca(2+) transients in ventricular and atrial cardiomyocytes. On electrical stimulation of ventricular myocytes, Ca(2+) concentration begins to rise earliest at the Z-line level and becomes uniform throughout the cytoplasm within about 10 ms after the onset of the action potential; transsarcolemmal Ca(2+) influx triggers Ca(2+) release from release sites on the junctional sarcoplasmic reticulum (SR) coupled to T-tubules at the Z-line throughout the cytoplasm. In atrial myocytes lacking the T-tubular network, transsarcolemmal Ca(2+) influx during an action potential triggers SR Ca(2+) release only at subsarcolemmal region. SR Ca(2+) release then spreads towards the central region of the cell through a propagated Ca(2+)-induced-Ca(2+) release mechanism. The atrio-ventricular difference in excitation-contraction coupling mechanisms underlies some of the atrio-ventricular difference in response to physiological and pharmacological stimuli.