Membrane potentials of respiratory neurones during dizocilpine-induced apneusis in adult cats

Abstract

1. In the vagotomized cat, blockade of NMDA receptors by dizocilpine (MK-801) produces an apneustic pattern of respiration characterized by a large increase in the duration of inspiration. 2. To identify dizocilpine-induced disfacilitations and disinhibitions in respiratory neurones generating the respiratory rhythm, membrane potential and input resistance of augmenting inspiratory (I; n = 11) and post-inspiratory (PI; n = 9) neurones were examined in the ventral respiratory group area, before and after administration of dizocilpine (0.1-0.3 mg kg-1 i.v.) in decerebrate, vagotomized, paralysed and artificially ventilated cats. 3. In I neurones, dizocilpine decreased the ramp depolarization and an 82% increase in input resistance was observed during inspiration. The inspiratory phase was prolonged, leading to a sustained level of depolarization during apneusis. The amplitude of stage 1 expiratory hyperpolarization decreased and its decay, which is normally slow, was faster. Throughout the remainder of expiration (stage 2) the membrane potential levelled off and the input resistance increased slightly (by 15%). 4. In PI neurones, dizocilpine depressed depolarization and suppressed firing in eight out of nine cells during the stage 1 expiratory phase. This was associated with a large (91%) increase of input resistance. The membrane potential switched quickly to stage 2 expiratory repolarization, during which a slight (19%) increase in input resistance occurred. 5. The hyperpolarization of PI neurones during early inspiration was reduced in amplitude by dizocilpine and input resistance was increased by 75% during inspiration, indicating that dizocilpine reduced the activity of the presynaptic inhibitory early-inspiratory (eI) neurones. 6. We conclude that NMDA receptor blockade in the respiratory network disfacilitates eI, I and PI neurones during their active phase. Decreased inhibitory processes during the inspiratory phase probably play a major role in the prolongation of inspiration.