LACTATE ACTIVATES ATP-SENSITIVE POTASSIUM CHANNELS IN GUINEA-PIG VENTRICULAR MYOCYTES

LACTATE ACTIVATES ATP-SENSITIVE POTASSIUM CHANNELS IN GUINEA-PIG VENTRICULAR MYOCYTES
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DOI:
10.1172/jci115497
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发表时间:
1991-11-01
影响因子:
15.9
通讯作者:
LI, Q
LI, Q
中科院分区:
医学1区
文献类型:
--
作者:
KEUNG, EC;LI, Q

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心肌ATP敏感钾通道的功能意义仍然存在争议,因为通道激活时ATP水平较低,而心肌缺血时ATP水平较高。我们使用全细胞膜片钳技术研究了(+)-乳酸对成年豚鼠心室肌细胞atp敏感钾通道的影响,乳酸在缺血期间由于糖酵解增加而大量积累。20 ~ 40 mM内液乳酸激活atp敏感钾通道,缩短动作电位持续时间。即使在内部溶液中存在2-5毫米ATP的情况下,通道的激活也会发生,并且依赖于细胞内游离镁的水平。我们的研究结果表明,即使ATP水平与中度至重度心肌缺血相似,细胞内乳酸也可能在激活心脏ATP敏感钾通道和缩短动作电位持续时间方面发挥重要作用。
The functional significance of cardiac ATP-sensitive potassium channels remains controversial because of the discrepancy between the low levels of ATP at which activation of the channels occurs and the much higher levels of ATP maintained during myocardial ischemia. We studied the effects of (+)-lactate, which accumulates in large quantity as a result of increased glycolysis during ischemia, on ATP-sensitive potassium channels in adult guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Lactate at 20-40 mM in the internal solution activated ATP-sensitive potassium channels and shortened action potential duration. Activation of the channels occurred even in the presence of 2-5 mM ATP in the internal solution and was dependent on intracellular free magnesium levels. Our results suggest that intracellular lactate may play a significant role in activating cardiac ATP-sensitive potassium channels and shortening action potential duration even at ATP levels similar to those resulting from moderate to severe myocardial ischemia.