School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
J Mol Cell Cardiol. 2023 Oct;183:70-80. doi: 10.1016/j.yjmcc.2023.09.002. Epub 2023 Sep 12.
The small conductance Ca-activated K current (I) is a potential therapeutic target for treating atrial fibrillation.
To clarify, in rabbit and human atrial cardiomyocytes, the intracellular [Ca]-sensitivity of I, and its contribution to action potential (AP) repolarisation, under physiological conditions.
Whole-cell-patch clamp, fluorescence microscopy: to record ion currents, APs and [Ca]; 35-37°C.
In rabbit atrial myocytes, 0.5 mM Ba (positive control) significantly decreased whole-cell current, from -12.8 to -4.9 pA/pF (P < 0.05, n = 17 cells, 8 rabbits). By contrast, the I blocker apamin (100 nM) had no effect on whole-cell current, at any set [Ca] (∼100-450 nM). The I blocker ICAGEN (1 μM: ≥2 x IC) also had no effect on current over this [Ca] range. In human atrial myocytes, neither 1 μM ICAGEN (at [Ca] ∼ 100-450 nM), nor 100 nM apamin ([Ca] ∼ 250 nM) affected whole-cell current (5-10 cells, 3-5 patients/group). APs were significantly prolonged (at APD and APD) by 2 mM 4-aminopyridine (positive control) in rabbit atrial myocytes, but 1 μM ICAGEN had no effect on APDs, versus either pre-ICAGEN or time-matched controls. High concentration (10 μM) ICAGEN (potentially I-non-selective) moderately increased APD and APD, by 5 and 26 ms, respectively. In human atrial myocytes, 1 μM ICAGEN had no effect on APD, whether stimulated at 1, 2 or 3 Hz (6-9 cells, 2-4 patients/rate).
I does not flow in human or rabbit atrial cardiomyocytes with [Ca] set within the global average diastolic-systolic range, nor during APs stimulated at physiological or supra-physiological (≤3 Hz) rates.
小电导钙激活钾电流（I）是治疗心房颤动的潜在治疗靶点。
在兔和人心房肌细胞中，明确 I 的细胞内[Ca]敏感性及其在动作电位（AP）复极中的作用，在生理条件下。
全细胞膜片钳、荧光显微镜：记录离子电流、AP 和 [Ca]；35-37°C。
在兔心房肌细胞中，0.5 mM Ba（阳性对照）显著降低全细胞电流，从-12.8 至-4.9 pA/pF（P<0.05，n=17 个细胞，8 只兔子）。相比之下，I 阻断剂 apamin（100 nM）在任何设定的 [Ca]（约 100-450 nM）下对全细胞电流均无影响。I 阻断剂 ICAGEN（1 μM：≥2 x IC）在该 [Ca]范围内也对电流无影响。在人心房肌细胞中，1 μM ICAGEN（在 [Ca]约 100-450 nM）和 100 nM apamin（在 [Ca]约 250 nM）均不影响全细胞电流（每组 5-10 个细胞，3-5 名患者）。阳性对照 2 mM 4-氨基吡啶显著延长兔心房肌细胞的 AP（在 APD 和 APD 处），但 1 μM ICAGEN 对 APD 无影响，与预 ICAGEN 或时间匹配对照相比。高浓度（10 μM）ICAGEN（可能为 I 非选择性）适度增加 APD 和 APD，分别增加 5 和 26 ms。在人心房肌细胞中，1 μM ICAGEN 对 APD 无影响，无论以 1、2 或 3 Hz（6-9 个细胞，2-4 个患者/频率）刺激。
在 [Ca]设定在全球平均舒张-收缩范围内的人心房肌细胞或兔心房肌细胞中，I 不流动，在生理或超生理（≤3 Hz）频率下刺激 AP 时也是如此。
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