- 1We investigated the role of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors and their regulation in affecting respiratory-related neurones in a neonatal rat medullary slice that spontaneously generates respiratory-related rhythm and motor output in the hypoglossal (XII) nerve.
- 2Bath application of the AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI) completely blocked XII nerve activity, as well as respiratory-related synaptic drives in neurones within the preBötzinger Complex (preBötC), site of rhythm generation in the slice.
- 3Local application of GYKI to the preBötC blocked respiratory rhythm. Local application of AMPA to the preBötC increased rhythm frequency and depolarized respiratory-related neurones.
- 4In the presence of tetrodotoxin (TTX), GYKI completely blocked the inward current induced by local application of AMPA, but not that induced by kainate.
- 5Local application of okadaic acid, a membrane-permeable inhibitor of phosphatase 1 and 2A, to the preBötC increased the frequency of respiratory motor discharge.
- 6Intracellular application of microcystin, a membrane-impermeable inhibitor of phosphatase 1 and 2A, enhanced endogenous inspiratory drive and exogenous AMPA-induced current (in the presence of TTX) in preBötC inspiratory neurones. Both the enhanced inspiratory drive and the increased AMPA-induced current were completely blocked by GYKI.
- 7We suggest that AMPA receptor activation and AMPA receptor modulation by phosphorylation are crucial for the rhythm generation within the preBötC.