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A fast and tiny current as common generator of slow regular pacemaking in brain and heart

Created on 31 Oct 2025

Authors

Fyon, A., Pavlova, O., Schaar, N., Mesirca, P., Brandoit, J., RInglet, S., Franci, A., Mangoni, M. E., Roeper, J., Drion, G., Seutin, V., Jehasse, K.

Abstract

Slow pacemaking is a key physiological process in specific excitable cells, yet its underlying mechanisms remain debated. Here we identify a conserved, voltage-dependent pacemaker current that is essential for slow, regular firing in both midbrain dopaminergic neurons and sinoatrial node cells. Conductance-based models incorporating this current reproduce stable pacemaking, requiring a fast-activating, small-amplitude current. This is further confirmed by dynamic-clamp experiments in dopaminergic neurons. Replacing the pacemaker current in a model with a voltage-independent conductance such as the non-selective sodium leak channels fails to sustain slow rhythmicity, highlighting the necessity for an adequate voltage dependence. Our results suggest a novel and shared biophysical mechanism for slow pacemaking in neuronal and cardiac systems

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 31 Oct 2025.

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