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

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
incorporating this current reproduce stable pacemaking, requiring a fast-activating,
small-amplitude current. Replacing the pacemaker current with a voltage independent conductance such as the non-selective sodium leak (NALCN) channels
fails to sustain slow rhythmicity, highlighting the necessity for an adequate voltage
dependence. Use of a modified Multi-Quadratic Integrate-and-Fire model shows
the geometric mechanism of the phenomenon. Our results suggest a novel and
shared biophysical mechanism of slow pacemaking in neuronal and cardiac
systems.