CHARACTERIZATION OF THE PACE-MAKER CURRENT KINETICS IN CALF PURKINJE-FIBERS
CHARACTERIZATION OF THE PACE-MAKER CURRENT KINETICS IN CALF PURKINJE-FIBERS
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DOI：
10.1113/jphysiol.1984.sp015114
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发表时间：
1984-01-01
影响因子：
5.5
通讯作者：
DIFRANCESCO, D
中科院分区：
文献类型：
--
作者：
DIFRANCESCO, D
用高K+、低Na+溶液研究了在电流时程与其他成分分离的条件下心脏起搏电流(IF)的动力学。在相对较大的负脉冲期间，IF的激活是S形的，并且近似为时间的三次幂指数函数。在接近激活曲线中间(-70/-80 mV)的电位下，发生了不太明显的S型激活。这里，考虑到非常慢的成分的存在，适应电流激活所需的功率接近1。在相同电位下的电流激活和失活之间的比较表明，虽然失活可以用单个指数来近似，但这两个过程具有非常不同的时间依赖性，这种差异取决于膜电位。这种行为与霍奇金-赫胥黎动力学不相容。当接近半激活范围时，电流以明显的单指数时间过程衰减，在较正的电位下，电流失活变为S形。至少需要指数的三次幂才能使其时间进程与.apprx的位势正相关。-40 mV。这些数据表明，打开和关闭状态都对应于几种不同的通道配置。在超极化过程中，通过在激活前应用大的、短的超极化来减少电流起始的延迟。适当的预脉冲持续时间和/或幅度可以将随后的电流激活降低到单一指数。具有和不具有预脉冲的记录并不总是重叠。在激活脉冲之前通过适当的超极化消除激活延迟后，可以通过施加给定幅度和可变持续时间的去极化来研究其恢复的时间过程。延迟恢复的时间进程似乎与在相同电压下记录的电流失活的时间进程无关。通过调节预超极化来减少激活延迟不影响在随后的去极化脉冲期间的电流衰减。电流衰减似乎仅取决于施加去激活脉冲之前达到的电流幅度。这一点以及上一段中的证据表明，延迟恢复和当前停用是两个独立的过程。根据实验测定的IF的动力学性质，提出了一种反应方案。通道模型由3种不同类型的5个门控单元组成，它们的运动并不都是独立的。通过实验数据拟合，确定了门控亚基的性质及其与电压的关系。该模型较好地预测了电流激活和失活的时间进程，以及在不同电压钳制方案下的动力学行为。讨论了该模型的目的和局限性，该模型仅被认为是一个描述性的模型。
Kinetics of the cardiac pace-maker current (if) were studied using high K+, low Na+ solutions under conditions where the current time course could be dissected from other components. Activation of if during relatively large negative pulses is S-shaped and is approximated by an exponential function of time to the 3rd power. Less-pronounced S-shaped activation occurs at potentials close to the middle of the activation curve (near-70/-80 mV). Here, allowing for the presence of a very slow component, the power required to fit the current activation approaches 1. The comparison between current activation and deactivation at the same potentials shows that although deactivation can be approximated by a single exponential, the 2 processes have a quite different time dependence and this difference depends on the membrane potential. This behavior is not compatible with Hodgkin-Huxley kinetics. While near the half-activation range the current decays with an apparently single exponential time course, at more positive potentials the current deactivation become sigmoidal. At least the 3rd power of an exponential is required to fit its time course at potentials positive to .apprx. -40 mV. These data imply that both open and closed states correspond to several distinct channel configurations. The delay in the current onset during a hyperpolarization is decreased by applying large, short hyperpolarizations before activation. Suitable pre-pulse durations and/or amplitudes can reduce the subsequent current activation to a single exponential. Records with and without a pre-pulse do not always superimpose. After the activation delay was removed by a suitable hyperpolarization preceding an activating pulse, the time course of its recovery can be studied by applying depolarizations of given amplitude and variable duration. The time course of the delay recovery does not seem to be linked to the time course of current deactivation recorded at the same voltage. Reduction of the activation delay by conditioning pre-hyperpolarizations does not affect current decay during a subsequent depolarizing pulse. The current decay appears to depend only on the current amplitude reached before a deactivating pulse is applied. This, and the evidence in the preceding paragraphy suggest that the delay recovery and the current deactivation are independent processes. A reaction scheme is proposed, which was developed on the basis of the experimentally determined kinetic properties of if. The channel model is composed of 5 gating subunits of 3 different types, not all independent in their movements. The properties of the gating subunits and their dependence on voltage was defined by experimental data fitting. The model satisfactorily predicts the current time course on activation and deactivation, and its kinetic behavior during different voltage-clamp protocols. The aim and limits of the proposed model, which is to be considered as only a descriptive one, are discussed.