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 preBötzinger complex (preBötC), 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.
Chevalier
Marc
M
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.
Ben-Mabrouk
Faiza
F
Tryba
Andrew K
AK
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D051379:Mice; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010507:Periodicity; D012119:Respiration; D012125:Respiratory Center / Q000033:anatomy & histology / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism
D015220:Calcium Channels; D015222:Sodium Channels; D012964:Sodium