Szigligeti P, Bányász T, Magyar J, Szigeti G, Papp Z, Varró A, Nánási P P
Department of Physiology, University Medical School of Debrecen, Hungary.
Acta Physiol Scand. 1998 Jun;163(2):139-47. doi: 10.1046/j.1365-201X.1998.00362.x.
The role of calcium current and changes in intracellular calcium concentration ([Ca2+]i) in regulation of action potential duration (APD) during electrical restitution process was studied in mammalian ventricular preparations. Properly timed action potentials were recorded from multicellular preparations and isolated cardiomyocytes using conventional microelectrodes and EGTA-containing patch pipettes. APD increased monotonically in canine and guinea pig ventricular preparations with increasing diastolic interval (DI), while in rabbit papillary muscles the restitution process was biphasic: APD first lengthened, then shortened as the DI increased. When the restitution process was studied in single cardiomyocytes using EGTA-containing patch pipettes, the restitution pattern was similar in the three species studied. Similarly, no difference was observed in the recovery time constant of calcium current (/Ca-L) measured under these conditions in voltage clamped myocytes. Loading the myocytes with the [Ca2+]i-chelator BAPTA-AM had adverse effects in rabbit and canine cells. In rabbit myocytes steady-state APD lengthened and the late shortening component of restitution was abolished in BAPTA-loaded cells. In canine myocytes BAPTA-load shortened steady-state APD markedly, and during restitution, APD decreased with increasing DI. The late shortening component of restitution, observed in untreated rabbit preparations, was greatly reduced after nifedipine treatment, but remained preserved in the presence of 4-aminopyridine or nicorandil. Beat to beat changes in APD, peak/Ca-L and [Ca2+]i, measured using the fluorescent dye, Fura-2, were monitored in rabbit ventricular myocytes after a 1-min period of rest. In these cells, the shortening of APD was accompanied by a gradual reduction of the peak/Ca-L and elevation of diastolic [Ca2+]i during the initial eight post-rest action potentials. It is concluded that elevation of [Ca2+]i shortens, while reduction of [Ca2+]i lengthens APD in rabbit, but not in canine ventricular myocytes. These differences may probably be related to different distributions of [Ca2+]i-dependent ion currents and/or to differences in calcium handling between the two species.
在哺乳动物心室标本中研究了钙电流及细胞内钙浓度（[Ca2+]i）变化在电恢复过程中对动作电位时程（APD）的调节作用。使用传统微电极和含乙二醇双四乙酸（EGTA）的膜片钳吸管从多细胞标本和分离的心肌细胞记录适时的动作电位。在犬和豚鼠心室标本中，随着舒张间期（DI）增加，APD单调增加，而在兔乳头肌中，恢复过程呈双相：随着DI增加，APD先延长，然后缩短。当使用含EGTA的膜片钳吸管在单个心肌细胞中研究恢复过程时，在所研究的三个物种中恢复模式相似。同样，在这些条件下电压钳制的心肌细胞中测量的钙电流（ICa-L）恢复时间常数未观察到差异。用[Ca2+]i螯合剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸乙酰甲酯（BAPTA-AM）加载心肌细胞对兔和犬细胞有不良影响。在兔心肌细胞中，BAPTA加载后稳态APD延长，恢复过程中的后期缩短成分消失。在犬心肌细胞中，BAPTA加载显著缩短稳态APD，并且在恢复过程中，APD随着DI增加而降低。硝苯地平处理后，在未处理的兔标本中观察到的恢复后期缩短成分大大减少，但在4-氨基吡啶或尼可地尔存在时仍保留。在兔心室肌细胞休息1分钟后，使用荧光染料Fura-2监测逐搏的APD、ICa-L峰值和[Ca2+]i变化。在这些细胞中，在最初的8个休息后动作电位期间，APD的缩短伴随着ICa-L峰值的逐渐降低和舒张期[Ca2+]i的升高。结论是，[Ca2+]i升高缩短兔心室肌细胞的APD，而[Ca2+]i降低则延长APD，但在犬心室肌细胞中并非如此。这些差异可能与[Ca2+]i依赖性离子电流的不同分布和/或两种物种之间钙处理的差异有关。
