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Persistent Sodium Current Is a Target for cAMP-Induced Neuronal Plasticity in a State-Setting Modulatory Interneuron

¹School of Life Sciences, Department of Biology and Environmental Sciences, University of Sussex, Falmer, Brighton, United Kingdom; ²Department of Experimental Zoology, Balaton Limnological Research Institute, Hungarian Academy of Sciences, Tihany, Hungary; and ³Medical Research Council Laboratory for Molecular and Cell Biology, University College London, London, United Kingdom

We have identified a TTX-resistant low-threshold persistent inward sodium current in the cerebral giant cells (CGCs) of Lymnaea, an important state-setting modulatory cell type of molluscan feeding networks. This current has slow voltage-dependent activation and de-activation kinetics, ultra-slow inactivation kinetics and fast de-inactivation kinetics. It activates at approximately –90 mV, peaks at approximately –30 mV, reverses at approximately +35 mV and does not show full voltage-dependent inactivation even at positive voltage steps. Lithium-sodium replacement experiments indicate that the persistent sodium current makes a significant contribution to the CGC membrane potential. Injection of cyclic adenosine monophosphate (cAMP) into the CGC cell body produces a large increase in the persistent sodium current that lasts for several hours. cAMP injection also leads to increased bursting, a significant decrease in the resistance and a significant depolarization of the soma membrane, indicating that cAMP-dependent mechanisms induce prolonged neuronal plasticity in the CGCs. Our observations provide the first link between cAMP-mediated modulation of a TTX-resistant persistent sodium current and prolonged neuronal plasticity in an identified modulatory cell type that plays an important role in behavioral state setting.

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