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NEUROSCIENCE |
1 Dipartimento di Scienze Fisiologiche-Farmacologiche Cellulari-Molecolari, Sezione di Fisiologia Generale e Biofisica Cellulare, Università degli Studi di Pavia, Via Forlanini 6, 27100 Pavia, Italy
2 Dipartimento di Biologia Evolutiva e Funzionale, Università degli Studi di Parma, Parco Area delle Scienze 11A, 43100 Parma, Italy
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 (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at 
–40 mV, showed half-maximal activation at –55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at –35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR 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 INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP 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.
(Received 1 February 2006;
accepted after revision 1 March 2006;
first published online 9 March 2006)
Corresponding author J. Magistretti: Dipartimento di Scienze Fisiologiche-Farmacologiche Cellulari-Molecolari, Sezione di Fisiologia Generale e Biofisica Cellulare, Università degli Studi di Pavia, Via Forlanini 6, 27100 Pavia, Italy. Email: jmlab1{at}unipv.it
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