MODELLING ELECTRICAL ACTIVITY OF CARDIOCYTE IN PULMONARY VEIN OF RABBIT

University of Oxford (2004) J Physiol 561P, PC11

Communications: MODELLING ELECTRICAL ACTIVITY OF CARDIOCYTE IN PULMONARY VEIN OF RABBIT

Leem,Chae Hun ; Seong,Hyeon Chan ; Youm,Jae Boum ; Kim,Won Tae ; Choe,Han ; Jang,Yeon Jin ; Park,Chun Sik ;

1. Department of Physiology, University of Ulsan College of Medicine, Seoul, South Korea. 2. Department of Physiology, Inje University College of Medicine, Pusan, South Korea.

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Atrial fibrillation is the most prevalent arrhythmia, however, the mechanisms of development of atrial fibrillation are not yet clear. Recently the most frequent source (over 90%) of paroxysmal atrial fibrillation is located inside main pulmonary veins. We isolated the cardiocyte from the main pulmonary vein of humanely killed rabbits and found these cells can generate spontaneous action potential. More interestingly, the increase of intracellular Na+ or Ca2+ accelerated the beating frequency, comapatible to atrial fibrillation (>5Hz). Therefore these cardiocytes may produce an ectopic activity for generating atrial fibrillation. We checked the electrical characteristics of these cardiocytes and tried to identify the mechanism of spontaneous action potential. Many different kinds of ionic channel activity were identified such as, INa, ICa,L, IKs, IK1, IKr, Incx, IK,ATP, IK,ACh, and ICl,Ca. We could not identify ICa,T, IST, and If, which are main currents for pace making activity of sinoatrial node cells. We tried to make the model of these cardiocyte to identify what is the main cause of spontaneous action potential. We used and tried to reconstruct many experimental observations. The measured membrane area (3907 μm2) was well matched to the capacitance value (39.4±3.3 pF, n=30), which suggested no existence of t-tubular system. Cytosolic application of 1 μM Ca2+ did not activate the Ca2+-activated Cl-current, which suggested that the cytosolic Ca2+ is compartmentalized. From the atrial myocytes and this experimental observations, we composed six compartments for Ca2+ regulation such as cytosolic, subsarcolemmal, junctional, junctional SR, central SR and network SR. We found the steady-state inactivation curve of L-type Ca2+ current was shifted to the negative potential which is a clear difference from ventricular myocytes. From these reconstructions, we found this shift of inactivation curve of L-type Ca2+ current, IKr and and Na+-Ca2+ exchange current probably participates in the generation of the spontaneous action potential.



Where applicable, experiments conform with Society ethical requirements.

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