Simultaneous activation of the small conductance calcium-activated potassium current by acetylcholine and inhibition of sodium current by ajmaline cause J-wave syndrome in Langendorff-perfused rabbit ventricles.
Simultaneous activation of the small conductance calcium-activated potassium current by acetylcholine and inhibition of sodium current by ajmaline cause J-wave syndrome in Langendorff-perfused rabbit ventricles.
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DOI：
10.1016/j.hrthm.2020.07.036
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发表时间：
2021-01
期刊：
影响因子：
5.5
通讯作者：
Chen PS
中科院分区：
文献类型：
--
作者：
Fei YD;Chen M;Guo S;Ueoka A;Chen Z;Rubart-von der Lohe M;Everett TH 4th;Qu Z;Weiss JN;Chen PS
在家兔心脏中，伴随着apamin敏感的小电导、钙激活钾电流（IKAS）激活和INa抑制诱导J波综合征（JWS）。JWS的猝死主要发生在夜间，当副交感神经张力强的时候。为了验证乙酰胆碱（ACh），副交感神经递质，激活IKAS和JWS的存在下，存在ajaI的假设。我们在Langendorff灌注的兔心脏中进行光学标测和全细胞电压钳以确定分离的心室肌细胞中的IKAS。ACh（1 μM）+阿义马林（2 μM）诱导所有（6名男性和6名女性）心脏的J点升高，从0.01± 0.01 mV升高至0.31 ± 0.05 mV（p<0.001），apamin（特异性IKAS抑制剂，100 nM）将其降低至0.14 ± 0.02 mV（p<0.001）。男性J点升高多于女性（p=0.037）。膜片钳研究表明，ACh显著（p<0.001）激活IKAS在分离的男性，但不是女性心室肌细胞（n=8）。光学标测结果显示，ACh引起的动作电位时程（APD）不均一性在右心室比左心室更明显。在ACh存在下，Apamin延长APD 25（p<0.001）和APD 80（p<0.001），并减弱APD异质性。Ajaxin进一步增加ACh诱导的APD不均一性。在ACh和阿曲库铵的存在下，6/6名男性和1/6名女性心脏（p= 0.015）诱导室性心律失常，在前者中，apamin可显著抑制室性心律失常。ACh激活心室IKAS。乙酰胆碱和阿曲库铵诱发J波综合征和促进诱发室性心律失常，男性多于女性。
Concomitant apamin-sensitive small conductance, calcium activated potassium current (IKAS) activation and INa inhibition induce J-wave syndrome (JWS) in rabbit hearts. Sudden death in JWS occurs predominantly in men at night, when parasympathetic tone is strong. To test the hypotheses that acetylcholine (ACh), the parasympathetic transmitter, activates IKAS and causes JWS in the presence of ajmaline. We performed optical mapping in Langendorff-perfused rabbit hearts and whole-cell voltage clamp to determine IKAS in isolated ventricular cardiomyocytes. ACh (1 μM) + ajmaline (2 μM) induced J-point elevations in all (6 male and 6 female) hearts from 0.01± 0.01 to 0.31 ± 0.05 mV (p<0.001), which were reduced by apamin (specific IKAS inhibitor, 100 nM) to 0.14 ± 0.02 mV (p<0.001). More J-point elevation was noted in males than females (p=0.037). Patch clamp studies showed that ACh significantly (p<0.001) activated IKAS in isolated male but not female ventricular myocytes (n=8). Optical mapping studies showed that ACh induced action potential duration (APD) heterogeneity, which was more significant in right than left ventricles. Apamin in the presence of ACh prolonged both APD25 (p<0.001) and APD80 (p<0.001), and attenuated APD heterogeneity. Ajmaline further increased APD heterogeneity induced by ACh. Ventricular arrhythmias were induced in 6/6 male and 1/6 female hearts (p= 0.015) in the presence of ACh and ajmaline, which was significantly suppressed by apamin in the former. ACh activates ventricular IKAS. ACh and ajmaline induce J-wave syndrome and facilitate the induction of ventricular arrhythmias more in male than female ventricles.
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影响因子：
20.1
作者：
Chua SK;Chang PC;Maruyama M;Turker I;Shinohara T;Shen MJ;Chen Z;Shen C;Rubart-von der Lohe M;Lopshire JC;Ogawa M;Weiss JN;Lin SF;Ai T;Chen PS
通讯作者：
Chen PS
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20.1
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1.5
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影响因子：
10.8
作者：
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通讯作者：
Jespersen, Thomas
影响因子：
4.8
作者：
Xu, YF;Tuteja, D;Chiamvimonvat, N
通讯作者：
Chiamvimonvat, N