Maintenance of eupnea of in situ and in vivo rats following riluzole: a blocker of persistent sodium channels.
We have proposed a "switching" concept for the neurogenesis of breathing in which rhythm generation by a pontomedullary neuronal circuit for eupnea may be switched to a medullary pacemaker system for gasping. This switch involves activation of conductances through persistent sodium channels. Based upon this proposal, eupnea should continue following a blockade of persistent sodium channels. In situ preparations of the decerebrate, juvenile rat were studied in normocapnia, hypocapnia and hypercapnia. Regardless of the level of CO(2) drive, riluzole (1-10 microM), a blocker of persistent sodium channels, caused increases in the frequency and reductions in peak integrated phrenic height. Even 20 microM of riluzole, a concentration four-fold higher than that which eliminates gasping, did not cause a cessation of phrenic discharge. In conscious, rats breathing continued unabated following intravenous administrations of 3-9 mgkg(-1) of riluzole. These administrations did cause sedation. We conclude that conductance through persistent sodium channels plays little role in the neurogenesis of eupnea.
St-John
Walter M
WM
Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Borwell Bldg, Lebanon, NH 03756, USA. walter.m.stjohn@dartmouth.edu
Waki
Hidefumi
H
Dutschmann
Mathias
M
Paton
Julian F R
JF
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003655:Decerebrate State / Q000503:physiopathology; D004576:Electromyography; D006935:Hypercapnia / Q000097:blood; D000860:Hypoxia / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D010791:Phrenic Nerve / Q000503:physiopathology; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology*; D012132:Respiratory Muscles / Q000502:physiology; D019782:Riluzole / Q000008:administration & dosage / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*
D026941:Sodium Channel Blockers; D002245:Carbon Dioxide; D019782:Riluzole