I-to and action potential notch are smaller in left vs right canine ventricular epicardium
I-to and action potential notch are smaller in left vs right canine ventricular epicardium
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DOI：
10.1152/ajpheart.1996.271.2.h548
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发表时间：
1996-08-01
影响因子：
4.8
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
DiDiego, JM;Sun, ZQ;Antzelevitch, C
复极化电流的跨壁异质性是许多物种心室心外膜、心内膜和M细胞电生理学和药理学显着差异的基础。左、右心室之间存在的不均匀性程度还没有得到很好的评价。本研究采用标准微电极和全细胞膜片钳技术，比较了犬右心室（RVE）和左心室（LVE）心外膜组织和心肌细胞的电生理特性和药理反应性。在几乎相同的条件下研究的RVE和LVE在动作电位的早期复极化阶段显示出重大差异。RVE中第1相的幅度几乎是LVE中的三倍：28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV（基本周期长度= 2，000 ms）。RVE的1相对刺激率和4-氨基吡啶（4-AP）的变化也更敏感，表明RVE中瞬时外向电流（I-1）的贡献比LVE大得多。4-AP加ryanodine、低氯化物或4，4 '-二异硫氰基芪-2，2'-二磺酸（氯化物通道阻滞剂）的组合完全消除了动作电位早期相的切迹和所有速率依赖性，使RVE和LVE难以区分。在+70 mV时，RVE肌细胞显示峰值I-至1密度在28至37 pA/pF之间。LVE肌细胞包括具有类似1，1密度的细胞（被认为代表亚表面细胞），但也包括具有小得多的电流水平的细胞（被认为代表表面细胞）。在电压大于或等于+10 mV时，LVE中的平均峰值I-对1密度显著小于RVE。我们的数据点显着的差异，在RVE的表面与LVE相比，在细胞中的I-1介导的动作电位缺口的大小，并表明，重要的区别可能存在于这两个组织的药理学试剂和病理生理状态的反应，如先前所证明的心外膜和内膜。我们的研究结果还表明，钙激活的外向电流有助于在RVE和LVE的早期复极阶段，这种电流的影响，虽然很小，是更重要的左心室。
Transmural heterogeneities of repolarizing currents underlie prominent differences in the electrophysiology and pharmacology of ventricular epicardial, endocardial, and M cells in a number of species. The degree to which heterogeneities exist between the right and left ventricles is not well appreciated. The present study uses standard microelectrode and whole cell patch-clamp techniques to contrast the electrophysiological characteristics and pharmacological responsiveness of tissues and myocytes isolated from right (RVE) and left canine ventricular epicardium (LVE). RVE and LVE studied under nearly identical conditions displayed major differences in the early repolarizing phases of the action potential. The magnitude of phase 1 in RVE was nearly threefold that in LVE: 28.7 +/- 6.2 vs. 10.6 +/- 4.1 mV (basic cycle length = 2,000 ms). Phase 1 in RVE was also more sensitive to alterations of the stimulation rate and to 4-aminopyridine (4-AP), suggesting a much greater contribution of the transient outward current (I-to 1) in RVE than in LVE. The combination of 4-AP plus ryanodine, low chloride, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (chloride channel blocker) completely eliminated the notch and all rate dependence of the early phases of the action potential, making RVE and LVE indistinguishable. At +70 mV, RVE myocytes displayed peak I-to 1 densities between 28 and 37 pA/pF. LVE myocytes included cells with similar 1,1 densities (thought to represent subsurface cells) but also cells with much smaller current levels (thought to represent surface cells). Average peak I-to 1 density was significantly smaller in LVE than in RVE at voltages more than or equal to +10 mV. Our data point to prominent differences in the magnitude of the I-to 1-mediated action potential notch in cells at the surface of RVE compared with the LVE and suggest that important distinctions may exist in the response of these two tissues to pharmacological agents and pathophysiological states, as previously demonstrated for epicardium and endocardium. Our findings also suggest that a calcium-activated outward current contributes to the early repolarization phase in RVE and LVE and that the influence of this current, although small, is more important in the left ventricle.