Voltage-gated ion channel diversity underlies neuronal excitability and nervous system evolution

Abstract

All nervous systems function via electrical excitability mediated by ion channels. However, channels and excitability are both ancient, preneuronal features that many cells use to rapidly adjust behavior. We systematically studied the evolutionary paths to neuronal excitability by characterizing the voltage-gated ion channel complements (VGL-chanomes) of 623 organisms, dissecting their expression patterns in 11 whole-body cell atlases and 3 entire nervous systems, and recording electrical properties of "primitive" neurons in the sea anemone. We find a disconnect between ion channel availability and organismal or nervous system complexity and find instead an association with lifestyle and behavior. Cell type restricted chanome expression predated the emergence of nervous systems in multicellular organisms. Multiple gene-family expansions and contractions independently specialized or diversified VGL-chanomes leading to a surprising convergent pattern: not the number of channels but their diversity and restrictive recruitment is a hallmark of neuronal complexity. These findings suggest that the evolution of highly complex nervous systems was not a stepwise progression of expanding complexity.