Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure

Abstract

Heart failure was associated with an increased cell size throughout the left ventricle, but the form of the changes in electrophysiology and Ca2+ transient were dependent on the myocyte sub-type. In particular sub-endocardial cells displayed markedly different changes compared to the other myocyte sub-types.

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

“…The epicardial cell has the shortest APD and the midmyocardial the longest, which is consistent with previous observations (Viswanathan et al, 1999;McIntosh et al, 2000;Gima and Rudy, 2002;Aslanidi et al, 2005;Sampson and Henriquez, 2005). Note also that the midmyocardial and epicardial action potentials are characterised with a notch that follows the upstroke; it is due to I to (McIntosh et al, 2000). Fig.…”

“…Experimental studies using isolated endocardial, midmyocardial and epicardial myocytes report transmural differences in I to in canine, rabbit, guinea pig and human (Li et al, 1998;McIntosh et al, 1998;Antzelevitch et al, 1999a, b), in I Na in canine (Antzelevitch et al, 1999a, b), in I Ks in canine and rabbit (Liu and Antzelevitch, 1995;Xu et al, 2001;Yan et al, 2001), and to a smaller extent, in I Kr in rabbit ). In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells.…”

“…In our study, transmural heterogeneities in ionic currents have been incorporated based on rabbit experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Xu et al, 2001), as done in a previous simulation study (Saucerman et al, 2004). Consistent with previous research (McIntosh et al, 1998(McIntosh et al, , 2000Viswanathan et al, 1999;Xu et al, 2001;Gima and Rudy, 2002;Idriss and Wolf, 2004;Saucerman et al, 2004;Sampson and Henriquez, 2005), our study shows that the transmural differences in ionic currents result in differences in the shape and duration of the action potential in epicardial, midmyocardial and endocardial cells. In isolated single cells, the presence of a prominent I to current in epicardial and midmycardial myocytes gives rise to a notch following the upstroke of the action potential, which is absent in endocardial action potentials (Fig.…”

“…Transmural ventricular heterogeneities in the transient outward potassium current (I to ), in the slow and rapid delayed rectifier potassium currents (I Ks , I Kr ), and in the sodium (I Na ) current were incorporated in the model based on experimental data (McIntosh et al, 1998(McIntosh et al, , 2000Dumaine et al, 1999;, as done previously (Saucerman et al, 2004). The above are the main currents responsible for transmural heterogeneities in action potential shape and duration.…”

“…Experimental studies of isolated ventricular tissue (Antzelevitch et al, 1999a, b;Idriss and Wolf, 2004), and of single myocytes isolated from various locations across the ventricular wall (McIntosh et al, 2000) have demonstrated that ionic properties change in the depth of the ventricular wall. In particular, three layers of functionally different cell types have been identified, namely the epicardial, endocardial, and midmyocardial layers (Ueda et al, 2004).…”