Taddese Abraha, Bean Bruce P
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Neuron. 2002 Feb 14;33(4):587-600. doi: 10.1016/s0896-6273(02)00574-3.
A role for "persistent," subthreshold, TTX-sensitive sodium current in driving the pacemaking of many central neurons has been proposed, but this has been impossible to test pharmacologically. Using isolated tuberomammillary neurons, we assessed the role of subthreshold sodium current in pacemaking by performing voltage-clamp experiments using a cell's own pacemaking cycle as voltage command. TTX-sensitive sodium current flows throughout the pacemaking cycle, even at voltages as negative as -70 mV, and this current is sufficient to drive spontaneous firing. When sodium channels underlying transient current were driven into slow inactivation by rapid stimulation, persistent current decreased in parallel, suggesting that persistent sodium current originates from subthreshold gating of the same sodium channels that underlie the phasic sodium current. This behavior of sodium channels may endow all neurons with an intrinsic propensity for rhythmic, spontaneous firing.
有人提出，“持续性”、阈下、对河豚毒素（TTX）敏感的钠电流在驱动许多中枢神经元的起搏活动中发挥作用，但这在药理学上一直无法进行测试。我们使用分离的结节乳头体神经元，通过以细胞自身的起搏周期作为电压指令进行电压钳实验，评估阈下钠电流在起搏活动中的作用。对TTX敏感的钠电流在整个起搏周期中都有流动，即使在低至 -70 mV的电压下也是如此，并且这种电流足以驱动自发放电。当通过快速刺激使瞬态电流的基础钠通道进入缓慢失活状态时，持续性电流也会平行下降，这表明持续性钠电流源自构成相位性钠电流基础的相同钠通道的阈下门控。钠通道的这种行为可能使所有神经元都具有节律性自发放电的内在倾向。
