[new preprint] A fast and tiny current as common generator of slow regular pacemaking in brain and heart
New collaborative work identifying a conserved pacemaker mechanism across neuronal and cardiac systems.
Excited to share our new collaborative preprint, now on bioRxiv!
The discovery
We identified a conserved pacemaker current that drives slow, regular firing in both midbrain dopamine neurons and heart pacemaker cells. Using a pharmacological blocker (XG), we found this current is essential - blocking it completely silences pacemaking across species (rodent, human) and systems (brain, heart).
The current has remarkable properties:
- Fast-activating (nearly instantaneous)
- Small amplitude but crucial
- Voltage-dependent activation starting around -50 mV
- Conserved across neuronal and cardiac cells
Modeling & validation
Our computational modeling (in Julia) showed that this small pacemaker conductance is sufficient for slow pacemaking, even in minimal models. Crucially, the voltage-dependence matters - replacing it with a linear leak cannot sustain stable slow pacemaking.
Dynamic-clamp experiments validated the model: injecting the modeled conductance into real neurons could silence, modulate, or rescue pacemaking as predicted.
Why it matters
This is the first demonstration of a shared pacemaker mechanism between brain and heart. It challenges existing theories (Ca²⁺ clock, NALCN channels) and reveals a fundamental principle: the most important currents can be the smallest ones.
Preprint: bioRxiv
Authors: Arthur Fyon, Oleksandra Pavlova, Nick Schaar, Pietro Mesirca, Julien Brandoit, Sofian Ringlet, Alessio Franci, Matteo E. Mangoni, Jochen Roeper, Guillaume Drion, Vincent Seutin, Kevin Jehasse
Contact: Kevin.Jehasse@uliege.be, afyon@uliege.be