Visualization of delayed Propagation of action potentials in Ca²⁺-overloaded ventricular muscles

Abstract

The two mechanisms can be candidates for ventricular arrhythmia in Ca²⁺-overloaded heart: (1) oscillation of membrane potential induced by frequent Ca²⁺ waves, resulting in triggered activity; (2) inhibition of gap junction channels which disturbs conductivity of action potentials (AP), resulting in increased probability of re-entry. In this study, we examined if propagation of APs are affected in situ in Ca²⁺ overloaded myocytes. Papillary muscles dissected from guinea pig ventricle were loaded with fluo-3 or rhod-2. Sequential fluorescence images of surface cells were obtained using the laser-scanning confocal microscope as reported previously (Kurebayashi et al. Am. J. Physiol. 287. C1646, 2004). In intact muscles, APs propagated without delay over a field of view of 300x300μm. In Ca²⁺-overloaded muscles which had been stimulated at a high frequency under anoxic condition, cells themselves were already less responsive to electrical stimulation and often showed AP alternans. Surprisingly, they sometimes showed a delay of ∼100ms in cell-to-cell propagation of APs. In the presence of a high concentration of heptanol, similar delay was observed. These results mean that conduction delays in several cells within a small area (∼0.5 x 0.5 mm) are enough to allow re-entry in Ca²⁺-overloaded heart. Inactivation of Na⁺ channels and/or inhibition of gap junctions may underlie the delayed conductivity. [Jpn J Physiol 55 Suppl:S105 (2005)]