Identification of Intracellular Signaling Cascades Mediating the PACAP-induced Increase in Guinea Pig Cardiac Neuron Excitability

摘要: The pituitary adenylate cyclase-activating polypeptide (PACAP) increases excitability of guinea pig cardiac neurons, an effect mediated through activation PAC1 receptors. signaling cascades that couple the receptor to alterations in membrane ionic conductances responsible for PACAP are unknown. Intracellular recordings were made from neurons kinase inhibitor-treated ganglia preparations determine which intracellular activated by stimulation mediate effect. In control cells, long depolarizing-current steps elicited one three action potentials. contrast, during application 10 nM PACAP, pulses multiple potential firing (greater than or equal five potentials) 79% neurons. Pretreatment with adenylyl cyclase inhibitor, SQ 22536 (100 µM), suppressed PACAP-induced increase excitability, whereas presence U-73122 (10 a potent phospholipase C (PLC) had no Thus, cyclase, but not PLC, was critical step mediating H-89 (1 protein A and PD 98059 (50 MEK also significantly blunted excitability. Furthermore, treatment forskolin (5 activator exposure cell-permeable cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP mM), partially recapitulated on We conclude downstream cAMP neuron