Li Q, Himmel H M, Ravens U
Institut fur Pharmakologie, Universitat-Gesamthochschule Essen, Germany.
J Cardiovasc Pharmacol. 1996 Mar;27(3):401-10. doi: 10.1097/00005344-199603000-00013.
Clofilium is an antiarrhythmic agent with a supposedly predominant class-III action which is related to impairment of K+ channel function. We investigated membrane currents in cardiac myocytes isolated from guinea pig ventricle to evaluate the selectivity of action of clofilium on K+ currents. For measurement of action potentials or membrane currents, the single electrode patch clamp technique was applied in current- or voltage-clamp mode, respectively. Clofilium (30 mu M) irreversibly prolonged the action potential duration in guinea pig myocytes. In contrast, the concomitant reduction in plateau phase was completely reversible. The delayed rectifier K+ current Ikappa, was reduced. The rapidly activating component of Ikappa, which has been defined by its sensitivity to the compound E-4031, was also reduced by clofilium. The inward rectifier was slightly inhibited by the drug. Clofilium reversibly reduced L-type Ca2+ current. Sodium current was inhibited in a use-dependent manner. This effect was not reversible but proceeded after washout of the compound. Therefore, clofilium affects both inward and outward currents in mammalian cardiac myocytes in a similar concentration range. The effects on multiple membrane currents may contribute to the antiarrhythmic action of the drug.
氯非铵是一种抗心律失常药物，据推测其主要具有Ⅲ类作用，这与钾通道功能受损有关。我们研究了从豚鼠心室分离的心肌细胞中的膜电流，以评估氯非铵对钾电流作用的选择性。为了测量动作电位或膜电流，分别在电流钳或电压钳模式下应用单电极膜片钳技术。氯非铵（30 μM）不可逆地延长了豚鼠心肌细胞的动作电位持续时间。相比之下，伴随的平台期缩短是完全可逆的。延迟整流钾电流Ikappa被降低。Ikappa的快速激活成分，已通过其对化合物E-4031的敏感性来定义，也被氯非铵降低。内向整流器被该药物轻微抑制。氯非铵可逆地降低L型钙电流。钠电流以使用依赖的方式被抑制。这种作用不可逆，但在冲洗掉该化合物后仍会持续。因此，氯非铵在相似的浓度范围内影响哺乳动物心肌细胞的内向和外向电流。对多种膜电流的影响可能有助于该药物的抗心律失常作用。
