van Borren Marcel M G J, Verkerk Arie O, Vanharanta Sakari K, Baartscheer Antonius, Coronel Ruben, Ravesloot Jan H
Department of Physiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Cardiovasc Res. 2002 Mar;53(4):869-78. doi: 10.1016/s0008-6363(01)00507-7.
Hypertrophied myocytes of failing hearts have prolonged action potential durations. It is unknown how the swelling-activated Cl(-) current (I(Cl,swell)) affects the abnormal AP configuration.
We studied I(Cl,swell) in ventricular myocytes isolated from failing and age-matched normal rabbit hearts. We applied whole-cell patch-clamp methodology and activated I(Cl,swell) by lowering tonicity of the superfusate.
Neither with ruptured-patch nor with amphotericin B perforated-patch, whole-cell clamp we found I(Cl,swell) active under isotonic conditions in either the normal or the hypertrophied failing heart (HFH) myocytes. I(Cl,swell) caused AP shortening and resting membrane potential (V(m)) depolarization in an osmotic gradient-dependent fashion. However, in the HFH myocytes swelling-induced AP changes were significantly smaller, even though the cells underwent the same relative change in planar cell surface area. Voltage-clamp experiments revealed that in HFH myocytes I(Cl,swell) current density was approximately 50% reduced.
Reduced I(Cl,swell) densities in HFH myocytes cause limited AP shortening and V(m) depolarization upon swelling of the cells.
衰竭心脏的肥大心肌细胞动作电位时程延长。目前尚不清楚肿胀激活的氯离子电流（I(Cl,swell)）如何影响异常的动作电位形态。
我们研究了从衰竭和年龄匹配的正常兔心脏分离的心室肌细胞中的I(Cl,swell)。我们应用全细胞膜片钳技术，通过降低灌流液的张力来激活I(Cl,swell)。
无论是在破膜模式还是两性霉素B穿孔膜全细胞钳模式下，我们都未发现在等渗条件下正常或肥大衰竭心脏（HFH）心肌细胞中的I(Cl,swell)有活性。I(Cl,swell)以渗透压梯度依赖的方式导致动作电位缩短和静息膜电位（V(m)）去极化。然而，在HFH心肌细胞中，肿胀诱导的动作电位变化明显较小，尽管细胞在平面细胞表面积上经历了相同的相对变化。电压钳实验表明，在HFH心肌细胞中，I(Cl,swell)电流密度降低了约50%。
HFH心肌细胞中I(Cl,swell)密度降低导致细胞肿胀时动作电位缩短和V(m)去极化受限。
