Lee Sherwin C, Hayashida Yuki, Ishida Andrew T
Section of Neurobiology, Physiology, and Behavior, University of California, Davis, California 95616-8519, USA.
J Neurophysiol. 2003 Dec;90(6):3888-901. doi: 10.1152/jn.00477.2003.
Spiking in central neurons depends on the availability of inward and outward currents activated by depolarization and on the activation and priming of currents by hyperpolarization. Of these processes, priming by hyperpolarization is the least described. In the case of T-type Ca2+ current availability, the interplay of hyperpolarization and depolarization has been studied most completely in expression systems, in part because of the difficulty of pharmacologically separating the Ca2+ currents of native neurons. To facilitate understanding of this current under physiological conditions, we measured T-type current of isolated goldfish retinal ganglion cells with perforated-patch voltage-clamp methods in solutions containing a normal extracellular Ca2+ concentration. The voltage sensitivities and rates of current activation, inactivation, deactivation, and recovery from inactivation were similar to those of expressed alpha1G (CaV3.1) Ca2+ channel clones, except that the rate of deactivation was significantly faster. We reproduced the amplitude and kinetics of measured T currents with a numerical simulation based on a kinetic model developed for an alpha1G Ca2+ channel. Finally, we show that this model predicts the increase of T-type current made available between resting potential and spike threshold by repetitive hyperpolarizations presented at rates that are within the bandwidth of signals processed in situ by these neurons.
中枢神经元的动作电位发放取决于去极化激活的内向和外向电流的可用性，以及超极化对电流的激活和预处理。在这些过程中，超极化预处理的描述最少。就T型Ca2+电流可用性而言，超极化和去极化的相互作用在表达系统中研究得最为透彻，部分原因是药理学上难以分离天然神经元的Ca2+电流。为了便于理解生理条件下的这种电流，我们在含有正常细胞外Ca2+浓度的溶液中，用穿孔膜片钳方法测量了分离的金鱼视网膜神经节细胞的T型电流。电流激活、失活、去激活以及从失活中恢复的电压敏感性和速率与表达的α1G（CaV3.1）Ca2+通道克隆相似，只是去激活速率明显更快。我们基于为α1G Ca2+通道开发的动力学模型，通过数值模拟重现了测量的T电流的幅度和动力学。最后，我们表明该模型预测了通过以这些神经元在原位处理的信号带宽内的速率进行重复超极化，在静息电位和动作电位阈值之间可获得的T型电流的增加。
