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Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ : an electrophysiological and modelling study
Author(s) -
Magistretti Jacopo,
Castelli Loretta,
Forti Lia,
D'Angelo Egidio
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.106682
Subject(s) - electrophysiology , biophysics , chemistry , patch clamp , sodium channel , nap , granule (geology) , conductance , voltage clamp , sodium , membrane potential , neuroscience , physics , biology , paleontology , organic chemistry , condensed matter physics
Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage‐dependent Na + currents. In this study we analysed voltage‐dependent Na + currents of rat cerebellar granule cells (GCs) by performing whole‐cell, patch‐clamp experiments in acute rat cerebellar slices. A transient Na + current ( I NaT ) was always present and had the properties of a typical fast‐activating/inactivating Na + current. In addition to I NaT , robust persistent ( I NaP ) and resurgent ( I NaR ) Na + currents were observed. I NaP peaked at ∼−40 mV, showed half‐maximal activation at ∼−55 mV, and its maximal amplitude was about 1.5% of that of I NaT . I NaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate I NaT , and showed voltage‐ and time‐dependent activation and voltage‐dependent decay kinetics. The conductance underlying I NaR showed a bell‐shaped voltage dependence, with peak at −35 mV. A significant correlation was found between GC I NaR and I NaT peak amplitudes; however, GCs expressing I NaT of similar size showed marked variability in terms of I NaR amplitude, and in a fraction of cells I NaR was undetectable. I NaT , I NaP and I NaR could be accounted for by a 13‐state kinetic scheme comprising closed, open, inactivated and blocked states. Current‐clamp experiments carried out to identify possible functional correlates of I NaP and/or I NaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with I NaR playing a role in their generation. Computer modelling showed that I NaR promotes DAP generation and enhances high‐frequency firing, whereas I NaP boosts near‐threshold firing activity. Our findings suggest that special properties of voltage‐dependent Na + currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially important consequences for cerebellar information transfer and computation.