Sodium channels implement a molecular leaky integrator that detects action potentials and regulates neuronal firing.

Autor:	Navarro MA; Division of Biological Sciences, University of Missouri, Columbia, United States., Salari A; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States., Lin JL; Division of Biological Sciences, University of Missouri, Columbia, United States., Cowan LM; Division of Biological Sciences, University of Missouri, Columbia, United States., Penington NJ; Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, United States., Milescu M; Division of Biological Sciences, University of Missouri, Columbia, United States., Milescu LS; Division of Biological Sciences, University of Missouri, Columbia, United States.; Department of Biology, University of Maryland, College Park, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2020 Feb 26; Vol. 9. Date of Electronic Publication: 2020 Feb 26.
DOI:	10.7554/eLife.54940
Abstrakt:	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. Competing Interests: MN, AS, JL, LC, NP, MM, LM No competing interests declared (© 2020, Navarro et al.)
Databáze:	MEDLINE
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