Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing
Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing
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DOI：
10.7554/elife.54940
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发表时间：
2020-02-26
期刊：
影响因子：
7.7
通讯作者：
Milescu, Lorin S.
中科院分区：
文献类型：
--
作者：
Navarro, Marco A.;Salari, Autoosa;Milescu, Lorin S.
电压门控钠通道在细胞兴奋性中起关键作用，它将微小的膜去极化放大为动作电位。与辅助亚单位和其他因素的相互作用改变了内在的动力学机制，导致新的分子和细胞功能。我们在这里展示了钠通道可以实现一个分子泄漏积分器，其中输入信号是膜电势，输出是长期失活状态的占有率。通过这一机制，钠通道有效地测量动作电位的频率，并将其转换为钠电流可利用性。反过来，Na+电流可以在负反馈环路中控制神经元的放电频率。因此，神经元对兴奋性输入的变化不那么敏感，并保持较低的放电率。我们在大鼠中缝5-羟色胺能神经元的背景下提出了这些想法，这些神经元以低频率自发放电，并为许多自主和认知大脑功能提供关键的神经调节。
Voltage-gated sodium channels play a critical role in cellular excitability, amplifying small membrane depolarizations into action potentials. Interactions with auxiliary subunits and other factors modify the intrinsic kinetic mechanism to result in new molecular and cellular functionality. We show here that sodium channels can implement a molecular leaky integrator, where the input signal is the membrane potential and the output is the occupancy of a long-term inactivated state. Through this mechanism, sodium channels effectively measure the frequency of action potentials and convert it into Na+ current availability. In turn, the Na+ current can control neuronal firing frequency in a negative feedback loop. Consequently, neurons become less sensitive to changes in excitatory input and maintain a lower firing rate. We present these ideas in the context of rat serotonergic raphe neurons, which fire spontaneously at low frequency and provide critical neuromodulation to many autonomous and cognitive brain functions.