The pacemaker current If in single human atrial myocytes and the effect of β‐adrenoceptor and A1‐adenosine receptor stimulation
The pacemaker current If in single human atrial myocytes and the effect of β‐adrenoceptor and A1‐adenosine receptor stimulation
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DOI：
10.1038/sj.bjp.0701473
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发表时间：
1997-11
影响因子：
7.3
通讯作者：
F. Porciatti;B. Pelzmann;E. Cerbai;P. Schaffer;R. Pino;E. Bernhart;B. Koidl;A. Mugelli
中科院分区：
文献类型：
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作者：
F. Porciatti;B. Pelzmann;E. Cerbai;P. Schaffer;R. Pino;E. Bernhart;B. Koidl;A. Mugelli
1我们用单个人心房肌细胞研究电流、特性和药理调节。采用大块酶消化法从心脏矫形手术患者的右心耳标本中获得细胞。2膜片钳全细胞形态的细胞与改良的泰氏液灌流，以减少干扰电流的污染，并放大If。平均细胞膜电容为85.0 6±2.4 1 pF(n=5 31)。数据与细胞几何尺寸(长94.2±1.89 μm，宽17.9±0.4 2 μm，n=12 6)基本一致。3当超极化至−12 0 mV时，2 5 2个细胞(82%)表现出超极化激活的内向电流(IF密度=3.77±0.2 5−pF 1)，当电流密度大于0.5 pA pF−1.4时，电流呈S形，符合玻尔兹曼模型；平均激活曲线(n=25)的最大电流幅度为205.97±19.94 pA，对应于3.87±0.63 pA pF−1，半最大激活电压(V1/2)出现在−86.68±2.19 mV，斜率−为11.39±0.69 mV。尾电流分析测得If的反转电位为−13.07±1.92 mV(n=6)。5在β肾上腺素受体激动剂异丙肾上腺素(Iso，1 μM)存在下，V1/2向较低负电压方向移动6.06±1.96 mV(n=16，P=0.0039)。选择性A1-腺苷受体激动剂环戊基腺苷(CPA，1 μM)使V1/2较对照曲线显著负移(−7.37±1.83 mV，P=0.0005，n=11)和1 μMISO存在时(−4.97±1.78，P=0.031，n=6)。虽然人心房组织中IF的病理生理学相关性仍有待确定，但我们的数据清楚地表明，它是通过刺激β-肾上腺素受体和A1-腺苷受体来调节的。
1We used single human atrial myocytes to studyIfoccurrence, properties and pharmacological modulation. Cells were obtained by chunk enzymatic digestion from samples of right atrial appendages of patients undergoing corrective cardiac surgery.2Patch‐clamped cells in the whole‐cell configuration were superfused with a modified Tyrode solution to reduce contamination by interfering currents and to amplifyIf. The average cell membrane capacitance was 85.06±2.41 pF (n=531). Data were consistent with the geometrical dimensions of the cells (length 94.2±1.89 μm, width 17.9±0.42 μm,n=126).3When hyperpolarizing to −120 mV from a holding potential of −40 mV, 252 of 306 tested cells (82%) expressed a hyperpolarization‐activated inward current (Ifdensity =3.77±0.25 pA pF−1); the current was considered to be present in a given cell if its density at −120 mV was larger than 0.5 pA pF−1.4Current activation was sigmoidal and fitted a Boltzmann model; the average activation curve (n=25) showed a maximum current amplitude of 205.97±19.94 pA, corresponding to 3.87±0.63 pA pF−1, voltage of half‐maximal activation (V1/2) at −86.68±2.19 mV and a slope of −11.39±0.69 mV. The reversal potential ofIfmeasured by tail‐current analysis was −13.07±1.92 mV (n=6). The addition of CsCl (5 mM) fully and reversibly blocked the current.5In the presence of the β‐adrenoceptor agonist isoprenaline (Iso, 1 μM), V1/2was significantly shifted toward less negative potentials by 6.06±1.96 mV (n=16,P=0.0039). The selective A1‐adenosine receptor agonist cyclopentyladenosine (CPA, 1 μM) caused a statistically significant shift of V1/2toward more negative potentials with respect to the control curve, both in the absence (−7.37±1.83 mV,P=0.0005,n=11) and in the presence of 1 μMIso (−4.97±1.78,P=0.031,n=6).6These results demonstrate that a current with the properties ofIfdescribed in cardiac primary and secondary pacemakers occurs in the majority of human atrial cells. While the pathophysiological relevance ofIfin human atrial tissue remains to be defined, our data clearly show that it is modulated through stimulation of β‐adrenoceptors and A1‐adenosine receptors.British Journal of Pharmacology(1997)122, 963–969; doi:10.1038/sj.bjp.0701473