{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Paul JR"],"funding":["NINDS NIH HHS"],"pagination":["13470"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5114562"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_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<sub>NaP</sub>). I<sub>NaP</sub> 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<sub>NaP</sub> affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane potential. Together, these results demonstrate a crucial link between the molecular circadian clock and electrical activity, providing examples of kinase regulation of electrical activity and the propagation of intracellular signals in neuronal networks."],"journal":["Nature communications"],"pubmed_title":["Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability."],"pmcid":["PMC5114562"],"funding_grant_id":["R01 NS082413","F31 NS086282"],"pubmed_authors":["DeWoskin D","Forger DB","Gamble KL","McMeekin LJ","Paul JR","Cowell RM"],"additional_accession":[]},"is_claimable":false,"name":"Regulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability.","description":"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<sub>NaP</sub>). I<sub>NaP</sub> 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<sub>NaP</sub> affects the action potential afterhyperpolarization, which increases the spontaneous firing rate without affecting the resting membrane potential. Together, these results demonstrate a crucial link between the molecular circadian clock and electrical activity, providing examples of kinase regulation of electrical activity and the propagation of intracellular signals in neuronal networks.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2025-04-25T19:23:18.96Z","creation":"2019-03-27T02:29:16Z"},"accession":"S-EPMC5114562","cross_references":{"pubmed":["27841351"],"doi":["10.1038/ncomms13470"]}}