Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
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豚鼠心室肌细胞中的时间依赖性向外电流。延迟整流器的门控动力学。
DOI：
10.1085/jgp.96.4.835
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发表时间：
1990-10
影响因子：
3.8
通讯作者：
RODEN, DM
中科院分区：
文献类型：
--
作者：
BALSER, JR;BENNETT, PB;RODEN, DM
几个相互矛盾的模型被用来描述心脏延迟整流器的门控行为。在这项研究中，在电压箝位的豚鼠心室肌细胞中测量了全细胞延迟整流电流，并确定了一个重现所观察到的动力学行为的最小模型。首先，使用旨在消除Na和Ca电流的外部溶液记录了-10和+70 mV之间的全细胞钾电流，并发现了两个随时间变化的外向电流分量。其中一个组分是La3（+）敏感电流，该电流灭活，类似于其他细胞类型中描述的瞬态外向电流；单通道观察证实在这些豚鼠心室细胞中存在瞬时外向电流（γ = 9.9 pS, [K]o = 4.5 mM）。尾振幅包络分析表明，在含有30-100微米La3+的溶液中不存在该成分。剩余的依赖时间的电流IK，以一个s型的时间过程被激活，这是由三个时间常数很好地表征。因此，将四态马尔可夫链模型（封闭-封闭-封闭-开放）与IK激活的非线性最小二乘拟合与先前用于表征IK门控的其他模型进行了比较：n2和n4 Hodgkin-Huxley模型以及只有两个封闭状态的马尔可夫链模型。四态模型在两种情况下均显著优于四态模型（P < 0.05）。霍奇金-赫胥黎模型未能充分描述宏观电流，这表明不应假设该K通道存在相同且独立的门控粒子。描述四态模型的速率常数的电压相关项，然后使用在宽电位范围（-80至+70 mV）内获得的IK数据的全局拟合方法导出。加入一个表示膜偶极力的项后，拟合度显著提高（P < 0.01）。所得速率常数预测在电压大于0 mV时，单通道开孔长（大于1s）。在细胞附着的贴片中，单个延迟整流通道在+60 mV （[K]o = 4.5 mM）下的平均弦导为5.4 pS，记录时间很短。这些通道表现出四态模型预测的行为：长开口和延迟峰的延迟分布。这些结果表明，心脏延迟整流器在打开去极化之前至少经历了两次主要的闭合状态转换。
Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outward current were found. One component was a La3(+)-sensitive current which inactivated and resembled the transient outward current described in other cell types; single-channel observations confirmed the presence of a transient outward current in these guinea pig ventricular cells (gamma = 9.9 pS, [K]o = 4.5 mM). Analysis of envelopes of tail amplitudes demonstrated that this component was absent in solutions containing 30-100 microM La3+. The remaining time- dependent current, IK, activated with a sigmoidal time course that was well-characterized by three time constants. Nonlinear least-squares fits of a four-state Markovian chain model (closed - closed - closed - open) to IK activation were therefore compared to other models previously used to characterize IK gating: n2 and n4 Hodgkin-Huxley models and a Markovian chain model with only two closed states. In each case the four-state model was significantly better (P less than 0.05). The failure of the Hodgkin-Huxley models to adequately describe the macroscopic current indicates that identical and independent gating particles should not be assumed for this K channel. The voltage- dependent terms describing the rate constants for the four-state model were then derived using a global fitting approach for IK data obtained over a wide range of potentials (-80 to +70 mV). The fit was significantly improved by including a term representing the membrane dipole forces (P less than 0.01). The resulting rate constants predicted long single-channel openings (greater than 1 s) at voltages greater than 0 mV. In cell-attached patches, single delayed rectifier channels which had a mean chord conductance of 5.4 pS at +60 mV ([K]o = 4.5 mM) were recorded for brief periods. These channels exhibited behavior predicted by the four-state model: long openings and latency distributions with delayed peaks. These results suggest that the cardiac delayed rectifier undergoes at least two major transitions between closed states before opening upon depolarization.
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DOI：
10.1085/jgp.58.4.413
发表时间：
1971-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Armstrong CM
通讯作者：
Armstrong CM
影响因子：
3.4
作者：
BALSER, JR;RODEN, DM;BENNETT, PB
通讯作者：
BENNETT, PB
影响因子：
3.4
作者：
CLAPHAM, DE;DEFELICE, LJ
通讯作者：
DEFELICE, LJ
影响因子：
3.8
作者：
HUME, JR;GILES, W
通讯作者：
GILES, W
影响因子：
5.5
作者：
BROWN, HF;CLARK, A;NOBLE, SJ
通讯作者：
NOBLE, SJ