Background sodium current underlying respiratory rhythm regularity

Rhythm-generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states - thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or 'stable' respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing. We used a mouse in vitro medullary slice preparation containing the rhythmogenic respiratory neural circuit, called the preBotzinger complex (preBotC), that underlies inspiratory respiratory activity. We varied either [K+](o) or [Na+](o), or blocked voltage-gated calcium channels, while recording from synaptically isolated respiratory pacemakers, and examined which of these manipulations resulted in their endogenous bursting becoming more irregular. Of these, lowering [Na+](o) increased the irregularity of endogenous bursting by synaptically isolated pacemakers. Lowering [Na+](o) also decreased the regularity of fictive eupneic activity generated by the ventral respiratory group (VRG) population and hypoglossal motor output. Voltage clamp data indicate that lowering [Na+](o), in a range that results in irregular population rhythm generation, decreased persistent sodium currents, but not transient sodium currents underlying action potentials. Our data suggest that background sodium currents play a major role in determining the regularity of the fictive eupneic respiratory rhythm.