HETEROGENEITY OF THE EARLY OUTWARD CURRENT IN VENTRICULAR CELLS ISOLATED FROM NORMAL AND HYPERTROPHIED RAT HEARTS
HETEROGENEITY OF THE EARLY OUTWARD CURRENT IN VENTRICULAR CELLS ISOLATED FROM NORMAL AND HYPERTROPHIED RAT HEARTS
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DOI：
10.1113/jphysiol.1993.sp019807
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发表时间：
1993-09-01
影响因子：
5.5
通讯作者：
LORENTE, P
中科院分区：
文献类型：
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作者：
BENITAH, JP;GOMEZ, AM;LORENTE, P
1.用全细胞电压钳技术，对大鼠心室肌细胞4-氨基吡啶敏感性早期外向电流（I（to））的性质、大小和动力学进行了研究。在每种拓扑类型的细胞中评估压力超负荷诱导的心肌肥厚对I（to）区域变化的调节作用。在室温（20-25 ℃）下，在膜两侧不存在Na+和存在3 mM CoCl 2的情况下进行电压钳实验。从-80 mV的保持电位研究I（to），并通过从不存在4-氨基吡啶（4-AP）的情况下获得的电流中减去在3 mM 4-氨基吡啶（4-AP）存在下由相同方案引起的总外向电流来确定I（to）。在正常心脏中，膜被动特性在每种地形类别的细胞中非常相似。我们的研究结果证实，大鼠心室肌细胞中主要的早期外向电流是4-AP敏感的，时间和电压依赖性的，并表明电流的大小在区域基础上变化：左心室游离壁细胞I（to）电流密度（+60 mV时为30.1+/-9.2 pA/pF）大于顶细胞（20.2+/-1.7 pA/pF）或隔膜细胞（11.9+/-3.3 pA/pF）。我们注意到左室游离壁的数据与其他区域相比具有更大的变异性。然而，计算得到的最大弦电导（μ S/pF）为：左心室游离壁细胞0.18+/-0.07，心尖细胞0.13+/-0.02，隔细胞0.08+/-0.02。这些发现可能反映了功能通道密度的差异分布。电压依赖性It.激活动力学没有差异，相对于地形。但隔区的失活时间常数较其他两组长.左心室肥厚是由腹主动脉缩窄引起的，并与正常大鼠的结果进行了比较。肥大细胞具有相似的静息电位，但比正常细胞更高的电容值。尽管I（to）幅度似乎没有改变，但电流密度-电压曲线略微向更正的电位移动，并且与正常细胞相比显著降低（单位为pA/pF，+60 mV）：左侧游离壁组为8.4+/-5.0，心尖组为11.6+/-2.0，隔组为3.8+/-1.5。稳态激活和失活参数没有明显改变，但动力学减慢.因此，我们的结论是，I（至）是差异分布在不同地区的正常大鼠心室，我们建议，这种区域的异质性可能与不同的分布功能通道密度，而不是在全细胞动力学或单通道特性的改变。压力超负荷引起的肥大降低I（至）。电流可用性通过降低电流密度而没有任何显着的变化，全细胞动力学，而一个离子分布的趋势是观察研究区域之间。肥大引起的变化的一个可能的解释可能是缺乏I（to）通道新生，导致每单位表面积通道密度降低。
1. The nature, magnitude and kinetics of the 4-aminopyridine-sensitive early outward current (I(to)) were analysed in isolated ventricular myocytes from the septum, the apex and the left ventricular free wall of rat ventricles using the whole-cell voltage clamp method. The modulatory effect of pressure overload-induced cardiac hypertrophy on the regional variations of I(to) was assessed in each topographical class of cells.2. Voltage clamp experiments were performed at room temperature (20-25-degrees-C) in the absence of Na+ on both sides of the membrane and in the presence of 3 mM CoCl2. I(to) was studied from a holding potential of -80 mV and determined by subtraction of total outward currents elicited by the same protocols in the presence of 3 mM 4-aminopyridine (4-AP) from those obtained in its absence.3. In normal hearts, membrane passive properties were very similar in each topographical class of cells. Our results confirmed that the predominant early outward current in rat ventricular cells was 4-AP-sensitive, time and voltage dependent, and demonstrated that the magnitude of the current varied on a regional basis: current density of I(to) in left ventricular free wall cells (30.1+/-9.2 pA/pF at +60 mV) was larger than in apex cells (20.2+/-1.7 pA/pF) or in septum cells (11.9+/-3.3 pA/pF). We noticed a larger variability in data from left ventricular free wall compared with other regions.4. No shift in steady-state voltage dependence of I(to) activation and inactivation was found. However, the maximal computed chord conductances were (in muS/pF): 0.18+/-0.07 for left ventricular free wall cells, 0.13+/-0.02 for apex cells, and 0.08+/-0.02 for septum cells. These findings might reflect a differential distribution in functional channel densities.5. No difference in voltage-dependent It. activation kinetics was present with respect to topography. However, inactivation time constants in septum were longer than those of both other groups.6. Left ventricular hypertrophy was induced by abdominal aortic constriction and its effects compared to the findings from normal rats. Hypertrophied cells had similar resting potentials but higher capacitance values than normal cells. Although I(to) magnitude appeared not to be modified, the current density-voltage curves were slightly shifted to more positive potentials and significantly decreased as compared to normal cells (in pA/pF, at +60 mV): 8.4+/-5.0 in the left free wall group, 11.6+/-2.0 in the apex group, and 3.8+/-1.5 in the septum group. Steady-state activation and inactivation parameters were not clearly modified, but kinetics were slowed down.7. We conclude, therefore, that I(to) is differentially distributed among different regions of the normal rat ventricle and we propose that this regional heterogeneity may be related to different distributions of functional channel densities, rather than alterations in whole-cell kinetics or single-channel properties. Pressure overload-induced hypertrophy reduces I(to). current availability by decreasing current densities without any significant change of whole-cell kinetics, while a homogenizing tendency of the ionic profile is observed among the studied regions. One possible explanation for the hypertrophy-induced variations may be an absence of I(to) channel neosynthesis, leading to a decrease of channel density per surface area unit.