SWELLING-INDUCED CHLORIDE-SENSITIVE CURRENT IN CANINE ATRIAL CELLS REVEALED BY WHOLE-CELL PATCH-CLAMP METHOD
SWELLING-INDUCED CHLORIDE-SENSITIVE CURRENT IN CANINE ATRIAL CELLS REVEALED BY WHOLE-CELL PATCH-CLAMP METHOD
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DOI：
10.1161/01.res.70.4.679
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发表时间：
1992-04-01
影响因子：
20.1
通讯作者：
SOROTA, S
中科院分区：
文献类型：
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作者：
SOROTA, S
在豚鼠和兔的心室肌细胞中检测到异丙肾上腺素诱导的氯电流，但在犬的心室细胞中未发现。这项调查是为了确定犬心房细胞是否具有这样的电流。用铯阻断的钾电流检测稳态电流。在全细胞膜片钳实验中，在膜片破裂后不久不能检测到异丙肾上腺素诱导的氯电流。然而，在没有异丙肾上腺素的情况下，随着贴片破裂后时间的推移，全细胞电流增加。自发激活的稳态电流以大约-25 mV的反转电位向外整流。随着时间的推移，形成的电流对细胞外氯化物浓度的变化很敏感，并被蒽-9-羧酸部分阻断。异丙肾上腺素可以增强这种电流的振幅。虽然使用了等渗移液管填充和细胞外溶液，但在全细胞膜片钳实验中发现，细胞肿胀是导致全细胞电导增加的原因。在细胞外溶液中加入50-75 mM甘露醇可以防止电流的发展和相关的细胞肿胀。当细胞外渗透压较低（221 mosm/kg）时，制霉菌素穿孔贴片记录可以观察到电流，而当细胞外溶液为等渗（293 mosm/kg）时，则不能观察到电流。心脏氯离子电流有可能使静息膜电位去极化并引起异常的自动性。氯离子电流也可以通过减少动作电位持续时间来缩短不应期。在与心肌肿胀相关的病理状态下，存在由肿胀引起的氯离子电流对于理解心电活动具有重要意义。
An isoproterenol-induced chloride current has been detected in ventricular myocytes from guinea pig and rabbit but has not been found in canine ventricular cells. This investigation was undertaken to determine whether canine atrial cells possessed such a current. Steady-state currents were examined with potassium currents blocked by cesium. In whole-cell patch-clamp experiments, an isoproterenol-induced chloride current could not be detected shortly after patch rupture. However, whole-cell current in the absence of isoproterenol increased over time after patch rupture. The spontaneously activating steady-state current was outwardly rectifying with a reversal potential of approximately -25 mV. The current that developed over time was sensitive to variation in extracellular chloride concentration and was partially blocked by anthracene-9-carboxylic acid. Isoproterenol could enhance the amplitude of this current once it developed. Although isosmotic pipette filling and extracellular solutions were used, cell swelling was found to be the cause of the increase in whole-cell conductance that was observed during whole-cell patch-clamp experiments. The development of the current and the associated cell swelling could be prevented with the addition of 50-75 mM mannitol to the extracellular solution. The current could be observed in perforated patch recordings with nystatin when extracellular osmolarity was low (221 mosm/kg) but not when the extracellular solution was isosmotic (293 mosm/kg). Cardiac chloride currents have the potential to depolarize the resting membrane potential and cause abnormal automaticity. Chloride currents can also decrease the refractory period through a reduction in action potential duration. The presence of a swelling-induced chloride current could be of importance for understanding cardiac electrical activity during pathological states that are associated with myocardial swelling.