TitleIonic conductances driving tonic firing in Purkinje neurons of larval zebrafish.
Publication TypeJournal Article
Year of Publication2025
AuthorsJadhav M.P', Verma S', Thirumalai V'
Journal Journal of Physiology
Date Published11 Sep 2025
ISSN0022-3751
Abstract

Purkinje neurons are critical for the functioning of the cerebellum, which is among the oldest and most conserved regions of the vertebrate brain. In mammals and in larval zebrafish, Purkinje neurons can generate tonic firing even when isolated from the network. Here we investigated the ionic basis of tonic firing in Purkinje neurons of larval zebrafish using voltage clamp for isolation of membrane currents along with pharmacology. We discovered that these neurons express L-type and P/Q-type high voltage-gated calcium currents, T-type low voltage-gated calcium currents and SK and BK-type calcium-dependent potassium currents. Among these, L-type calcium currents and SK-type calcium-dependent potassium currents were indispensable for tonic firing, while blocking T-type, P/Q-type and BK currents had little effect in comparison. We observed that action potentials were broadened when either L-type or SK channels were blocked. Based on these results, we propose that calcium entry via L-type calcium channels activates SK potassium channels leading to faster action potential repolarization, in turn aiding the removal of inactivation of sodium channels. This allows larval zebrafish Purkinje neurons to continue to fire tonically for sustained periods. In mammals also, tonic firing in Purkinje neurons is driven by calcium channels coupling to calcium-dependent potassium channels, yet the specific types of channels involved are different. We therefore suggest that coupling of calcium channels and calcium-dependent potassium channels could be a conserved mechanism for sustaining long bouts of high frequency firing.

DOI10.1113/JP286063