Alteration of medullary respiratory unit discharge by iontophoretic application of putative neurotransmitters.

1 Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non-respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied gamma-aminobutyric acid (GABA), acetylcholine (ACh) and glutamate. 2 GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non-respiratory units. Some phase-spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non-respiratory neuronal activities. 3 While application of ACh or glutamate induced continuous firing in phasic, phase-spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity. 4 These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active-inhibitory phase-switching mechanisms serve to define respiratory rhythmicity.