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 CO2 drive, riluzole (1–10 μM), a blocker of persistent sodium channels, caused increases in the frequency and reductions in peak integrated phrenic height. Even 20 μM 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 mg kg−1 of riluzole. These administrations did cause sedation. We conclude that conductance through persistent sodium channels plays little role in the neurogenesis of eupnea.