AMPA RECEPTOR ACTIVATION AND PHOSPHATASE INHIBITION AFFECT NEONATAL RAT RESPIRATORY RHYTHM GENERATION

1. We investigated the role of pha-amino-3-hydroxy-5-methylisoxazole-4 -propionate (AMPA) receptors and their regulation in affecting respira tory-related neurones in a neonatal rat medullary slice that spontaneo usly generates respiratory-related rhythm and motor output in the hypo glossal (XII) nerve. 2. Bath application of the AMPA receptor antagoni st -4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI) completel y blocked XII nerve activity, as well as respiratory-related synaptic drives in neurones within the preBotzinger Complex (preBotC), site of rhythm generation in the slice. 3. Local application of GYKI to the pr eBotC blocked respiratory rhythm. Local application of AMPA to the pre BotC increased rhythm frequency and depolarized respiratory-related ne urones. 4. In the presence of tetrodotoxin (TTX), GYKI completely bloc ked the inward current induced by local application of AMPA, but not t hat induced by kainate. 5. Local application of okadaic acid, a membra ne-permeable inhibitor of phosphatase 1 and 2A, to the preBotC increas ed the frequency of respiratory motor discharge. 6. Intracellular appl ication of microcystin, a membrane-impermeable inhibitor of phosphatas e 1 and 2A, enhanced endogenous inspiratory drive and exogenous AMPA-i nduced current (in the presence of TTX) in preBotC inspiratory neurone s. Both the enhanced inspiratory drive and the increased AMPA-induced current were completely blocked by GYKI. 7. We suggest that AMPA recep tor activation and AMPA receptor modulation by phosphorylation are cru cial for the rhythm generation within the preBotC.