Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability.

ABSTRACT: How neurons encode intracellular biochemical signalling cascades into electrical signals is not fully understood. Neurons in the central circadian clock in mammals provide a model system to investigate electrical encoding of biochemical timing signals. Here, using experimental and modelling approaches, we show how the activation of glycogen synthase kinase 3 (GSK3) contributes to neuronal excitability through regulation of the persistent sodium current (I_NaP). I_NaP exhibits a day/night difference in peak magnitude and is regulated by GSK3. Using mathematical modelling, we predict and confirm that GSK3 activation of I_NaP affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane pot

SUBMITTER: Paul JR 

PROVIDER: S-EPMC5114562 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature