INTRACELLULAR SIGNAL PATHWAYS CONTROLLING RESPIRATORY NEURONS

Medullary respiratory neurons are influenced by a variety of neuromodu lators, but there is a lack of information about the specific intracel lular signal pathways involved. In this report we describe the modulat ory effects of the cyclic adenosine-triphosphate (cAMP)-dependent prot ein kinase and of protein kinase C pathways on voltage- and ligand-con trolled ionic conductances and demonstrate their functional significan ce in regulating the excitability of medullary respiratory neurons of the vivo cat. Evidence is presented that PKA and PKC pathways are pers istently activated. PKA regulates current flow through persistently ac tivated and GABA(B) receptor-controlled potassium channels as well as GABA(A) receptor-controlled chloride channels. PKC also depresses pers istent potassium currents but it potentiates excitatory and inhibitory synaptic currents. The clinical significance of these intracellular s ignal pathways is demonstrated in a case of a child suffering from apn eustic breathing, who was successfully treated with a 5HT-1A receptor agonist. (C) 1997 Elsevier Science B.V.