Lithium modulates cortical excitability in vitro

Brain Research
Charlotte Butler-MunroPhilip M Heyward

Abstract

The sometimes devastating mood swings of bipolar disorder are prevented by treatment with selected antiepileptic drugs, or with lithium. Abnormal membrane ion channel expression and excitability in brain neurons likely underlie bipolar disorder, but explaining therapeutic effects in these terms has faced an unresolved paradox: the antiepileptic drugs effective in bipolar disorder reduce Na(+) entry through voltage-gated channels, but lithium freely enters neurons through them. Here we show that lithium increases the excitability of output neurons in brain slices of the mouse olfactory bulb, an archetypical cortical structure. Treatment in vitro with lithium (1 to 10mM) depolarizes mitral cells, blocks action potential hyperpolarization, and modulates their responses to synaptic input. We suggest that Na(+) entry through voltage-gated channels normally directly activates K(+) channels regulating neuron excitability, but that at therapeutic concentrations, lithium entry and accumulation reduces this K(+) channel activation. The antiepileptic drugs effective in bipolar disorder and lithium may thus share a membrane target consisting of functionally coupled Na(+) and K(+) channels that together control brain neuron excitability.

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Citations

Jul 6, 2014·Human Molecular Genetics·Kevin A StraussErik G Puffenberger
Aug 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Qi WuRichard D Palmiter
Mar 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Isabella Farhy TselnickerNathan Dascal
Sep 16, 2016·Oxidative Medicine and Cellular Longevity·Antonina LucaMaria Luca
Sep 9, 2017·Metallomics : Integrated Biometal Science·Magali Roux, Anthony Dosseto
Jan 15, 2021·Medical Hypotheses·Kohji Sato
May 1, 2021·International Journal of Molecular Sciences·Santosh RijalSeong Kyu Han
Aug 7, 2021·Cellular and Molecular Neurobiology·Enrique L M Ochoa

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