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

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 becames 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 thourgh a propagated Ca 2+-induced-Ca 2+ release mechanism. The atrio-ventricular difference in excitation-contraction coupling mechanisms underlies some of the atrioventricular difference in response to physiological and pharmacological stimuli.

Calcium signalling during excitation-contraction coupling in mammalian atrial myocytes

“…4B). Similar results have been obtained using atrial cells from different mammalian species, including rat (Mackenzie et al, 2001;Tanaka et al, 2003;Woo et al, 2002), guinea pig (Berlin, 1995;Lipp et al, 1990), cat Kockskamper et al, 2001;Sheehan and Blatter, 2003) and human (Hatem et al, 1997). These studies all agree that atrial Ca 2+ responses originate at subsarcolemmal sites and that the Ca 2+ signals have the greatest amplitude and rate of rise in the peripheral initiation zone.…”

“…This means that even those Ca 2+ spark sites deep within a ventricular cell are recruited during EC coupling, thereby giving rise to a synchronised global Ca 2+ signal (Brette et al, 2005). If ventricular myocytes are imaged at high speed during the onset of EC coupling, the Ca 2+ signal can be seen to arise with a striated appearance (Cleemann et al, 1998;Tanaka et al, 2003). This reflects the initiation of Ca 2+ release adjacent to the T-tubules before the Ca 2+ signal has managed to diffuse from the dyadic junctions (Isenberg et al, 1996).…”

Differential gene expressions in atrial and ventricular myocytes: insights into the road of applying embryonic stem cell-derived cardiomyocytes for future therapies

“…In contrast, in ventricular myocytes of small rodents, the earliest rise in calcium level occurs in the Z-line upon arrival of the action potential (190), although this nonuniform calcium rise lasts for a very short period of time (around 4 ms). As the ventricular myocytes contain T-tubules, which serve to bring VGCCs on the cell surface membrane and RyRs on the SR into close proximity, the rise in calcium level becomes uniform throughout the cytoplasm in a rapid and global manner (within 10 ms after the onset of the action potential) (190).…”

“…There are significant differences in the E-C coupling between atrial and ventricular myocytes; in small rodents, the differences are mostly due to cellular ultrastructure differences caused by the absence/low abundance of transverse tubules (T-tubules; the T-tubular invaginations of the cell surface plasma membrane) in atrial myocytes and their presence in ventricular myocytes (19,190). In atrial myocytes of small rodents where the T-tubules are poorly developed or absent, meaning that the cell surface plasma membrane does not regularly protrude into the center of the atrial myocytes, the calcium influx through the cell surface membrane will trigger CICR through the RyRs located in the subsarcolemmal region.…”

“…Therefore, depolarization leads to an increase in calcium signals that originates mostly at the cell periphery (19), leading to a "shell" of increased calcium level immediately beneath the cell surface membrane, with no immediate response deeper inside the cells (19). This CICR will then spread toward the center of the atrial myocytes by a propagated mechanism (190). However, this propagated CICR does not happen all the time because the subsarcolemmal calcium signal does not spread in a fully regenerative manner.…”