Background sodium current stabilizes bursting in respiratory pacemaker neurons.
Endogenous pacemaker properties have been proposed to generate rhythmic activity underlying many behaviors including respiration. For pacemakers to generate regenerative bursting, background currents maintain their membrane potential (Vm) within a range where bi-stable properties are expressed, thereby stabilizing rhythmogenesis. We previously found that the baseline Vm of respiratory pacemakers is stabilized against hyperpolarizing shifts in their Vm. In response to prolonged hyperpolarizing current injection synaptically isolated respiratory pacemakers steadily depolarize and resume bursting, suggesting a stabilizing background current is involved. What is the ionic basis of this background current in respiratory pacemakers? Here we demonstrate that in low-[Na(+)](o) ACSF, synaptically isolated respiratory pacemakers hyperpolarized and remained outside the bursting window, but could burst upon depolarizing current injection. These data suggest that pacemakers possess a background sodium current that is necessary to bring their Vm into a bursting range. Low-[Na(+)](o) ACSF also abolished the depolarizing shift evoked during prolonged hyperpolarizing current injection, and bursting did not resume. This depolarizing shift persisted in the presence of I(h)-current blockers, but was abolished in tetrodotoxin. Although, under control conditions, the Vm of synaptically isolated respiratory pacemaker neurons was not significantly affected when [K(+)](o) was changed from 3 to 8 mM, the Vm is altered when [K(+)](o) was raised in low-[Na(+)](o) ACSF. Thus, current-clamp studies suggest that respiratory pacemaker neurons possess a background sodium current that maintains their membrane potential within a range where they express bursting, thereby stabilizing rhythmogenesis.
The University of Chicago, Department of Organismal Biology, 1027 E. 57th Street, Chicago, Illinois 60637, USA. Tech10s@techsan.org
Andrew K
AK
Tryba
Jan-Marino
JM
Ramirez
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012125:Respiratory Center / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D012964:Sodium / Q000172:deficiency / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium