Source and Action of Pituitary Adenylate Cyclase-Activating Polypeptide in Guinea Pig Intrinsic Cardiac Ganglia

The mammalian parasympathetic cardiac ganglia form a complex intrinsic cardiac nervous system presumed to contain multiple neuron types and are innervated by extrinsic fibers from multiple sources, each containing specific neurotransmitters and neuropeptides. In the guinea pig, the preganglionic parasympathetic cholinergic fibers contain the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), and essentially all cardiac neurons express the PACAP selective PAC1 receptor. Application of exogenous PACAP depolarizes and enhances the excitability of guinea pig cardiac neurons. The mechanism by which PACAP enhances excitability is not established. However, Ca2+ influx through PACAP-activated nonselective cation channels is required for the PACAP-induced increase in excitability of guinea pig cardiac neurons. In addition, a PACAP-induced shift in the voltage dependence of activation of the cyclic nucleotidegated, hyperpolarization-activated current, Ih, most likely participates in the peptide-induced increase in neuronal excitability. The release of endogenous PACAP by repetitive stimulation of preganglionic fibers in vitro contributes to the generation of a slow excitatory postsynaptic potential and also can enhance cardiac neuron excitability. We hypothesize that PACAP released during ongoing vagal activity may regulate cardiac neuron excitability in vivo.