Comparison of contraction and calcium handling between right and left ventricular myocytes from adult mouse heart: a role for repolarization waveform

Abstract

In the mammalian heart, the right ventricle (RV) has a distinct structural and electrophysiological profile compared to the left ventricle (LV). However, the possibility that myocytes from the RV and LV have different contractile properties has not been established. 2+ influx and myocyte shortening were larger in response to the LVendo AP, independent of myocyte subtypes. Evaluation of possible regional differences in myocyte Ca 2+ handling was based on: (i) the current-voltage relation of the Ca 2+ current; (ii) sarcoplasmic reticulum Ca 2+ uptake; and (iii) mRNA expression of important components of the Ca 2+ handling system. None of these were significantly different between RV and LVendo. In contrast, the Ca 2+ -independent K + current, which modulates AP repolarization, was significantly different between RV, LVepi and LVendo. These results suggest that these differences in K + currents can alter AP duration and modulate the [Ca 2+ ] i transient and corresponding contraction. In summary, these findings provide an initial description of regional differences in excitation-contraction coupling in the adult mouse heart. Evidence that the AP waveform is an important causative factor for these differences is presented. In hearts from adult mammals, right (RV) and left (LV) ventricles have distinctive structural and contractile characteristics as well as heterogeneous electrophysiological properties (Katz, 2001). The RV pumps blood into the relatively low-pressure pulmonary vasculature. Accordingly RV chamber pressures are much lower and the workload of the right ventricle (RV) differs significantly from that of the left ventricle (LV). In addition, the mechanical afterload in the right ventricle is significantly smaller. Consistent with these physiological differences, the free wall of the RV is much thinner than that of the LV. Systematic electrophysiological studies have also shown that the mammalian ventricle exhibits a well-defined heterogeneity of AP waveforms. In adult mice and rats, the AP duration (APD) at a fixed heart rate is shorter in the RV than in the LV (Watanabe et al.

The effect of repolarization duration on the indices of the pump function of the heart ventricles in animals with different types of activation of the myocardium under ectopic excitation of ventricles

“…Besides, relative to "slow" muscle Са 2+ transition to a faster virtual muscle has a rapid contraction and shorter duration of action potential. At the same time, pacing of the "fast" muscle reduces the contractility of the myocardium, but pacing of the "slow" onechanges insignificantly [30,[34][35][36]. Thus, we can assume that the electrical pacing of the ventricular area with longer ARIs does not change the contractility, while pacing of the ventricular area with shorter ARIs leads to the reduction of the pump function of the heart.…”

Cardiac troponin T mutations promote life-threatening arrhythmias

“…Since this Ca 2+ influx is the "trigger" for Ca 2+ release from the sarcoplasmic reticulum, the intracellular Ca 2+ transient is decreased substantially by action potential shortening in the mammalian heart (17,18). It is also known that this pattern of events differs significantly between myocytes from the right versus the left ventricle in the adult mouse heart (19). The decreased action potential duration reported by Baudenbacher et al (3) would be predicted to result in a significant decrease in contractile strength or negative inotropic effect.…”

Characterization and mechanism of P2X receptor-mediated increase in cardiac myocyte contractility

“…Myocyte CS by changes in sarcomere length and Ca 2ϩ transients were recorded simultaneously from single isolated myocytes with an epifluorescence inverted microscope with Ionoptix software and camera (Ionoptix, Milton, MA) as previously described (5,6,10,12). Cells were superfused with Tyrode's solution at 25°C and field stimulated as previously described (21).…”

“…2-meSATP and ATP were obtained from Sigma Chemical (St. Louis, MO). Fura 2-AM was obtained from Molecular Probes (Eugene, OR) and used according to manufacturer's instructions as previously described (5,6,10,12). cAMP EIA kit was from GE Healthcare (Piscataway, NJ).…”

“…Steady-state recordings were measured under baseline control conditions and after exposure to 2-meSATP. Various CS and Ca 2ϩ transient parameters such as amplitude, maximal rates of rise and fall, time to 50% peak, and time to 50% decline were measured with Ionoptix curve-fitting algorithm software as previously described (5,6,12,13).Cyclic AMP was determined with an enzymatic immunoassay kit according to manufacturer's instructions, similar to the method used to estimate cAMP level in dispersed mammalian cardiac ventricular myocytes (28,14). In brief, myocytes were isolated and plated in a 96-well plate at a density of 10 3 cells/well.…”