Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC272

Poster Communications

IP3 sensitive, Ca2+-dependent oscillating currents in cardiac myocytes of pulmonary vein of rabbit

J. Kwon1, W. Kim1, J. Lee1, H. Kim1, H. Baek1, C. Leem1

1. Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea, Republic of.


Atrial fibrillation (AF) is the most common kind of arrhythmia, however, its etiology is still obscure. Pulmonary veins (PVs) were found to be important ectopic foci for the initiation and maintenance of AF. Previous report suggested that Ca2+ dysregulation induced by ryanodine and rapid pacing in PVs caused the arrhythmogenic activity (Honjo et al., 2003). We enzymatically isolated single cardiac myocytes in pulmonary vein of rabbit. All procedures were accorded with national legislation. Using whole cell voltage clamping technique, we found oscillating outward currents activated by step depolarization pulses. The oscillating outward currents were Cl--dependent and abolished by the removal of intracellular Ca2+ changes with ethyleneglycol-bis-(β-aminoethylether)-N,N,N',N'-tetraacetic acid or 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. The frequency of the oscillating current was increased as intracellular [Na+] increased. One of the interesting features was that those currents became activated by serial application of step depolarization pulses to +60 mV (1 sec duration, 30 sec intervals) and the oscillating current was transiently remained at the holding potential, -40 mV as an inward current. When depolarizing step pulses were applied repeatedly, the remaining time of the oscillating currents at the holding potential became longer and finally continuously activated. Those inward oscillating currents certainly act as a depolarization force and may cause arrhythmogenic activity. The oscillating currents were not observed in atrial cardiac myocytes in atrial appendage. We tested IP3 dependency of the oscillating currents. We found IP3-sensitive Ca2+ release blockers such as heparin and 2-aminoethoxydephenyl borate (2-APB) blocked the oscillating currents. And also phospholipase C inhibitor, U73122, abolished the oscillating current activation. Those results suggested that the oscillating currents may be dependent on [IP3]i oscillation. In conclusion, the cardiac myocytes in PV can initiate arrhythmogenic Ca2+-dependent oscillating currents activated by intracellular Ca2+ loading and IP3-dependent Ca2+ release.

Where applicable, experiments conform with Society ethical requirements