TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia

Tachykinins depolarize guinea pig intracardiac neurons by activating nonselective cationic channels. Recently, members of the transient receptor potential family of membrane channels (TRPC) have been implicated in the generation of G protein-coupled receptor-activated nonselective cationic currents. We have investigated whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited immunoreactivity to TRPC6. After culture of cardiac ganglia whole-mount explants for 72 hours, the TRPC6-IR fiber networks were absent. Therefore, the TRPC6-IR fibers were derived from sources extrinsic to the heart. A small percentage (similar to3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity in control preparations, and the percentage of cells exhibiting TRPC6 immunoreactivity was not changed following explant culture for 72 hours. The few intrinsic TRPC6-IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of TRPC6-IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The TRPC6-IR fibers were not immunoreactive for choline acetyltransferase, tyrosine hydroxylase, or substance P. However, the TRPC6-IR fibers exhibited immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6-IR fibers within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that also contain NOS. We found, in support of this conclusion, that TRPC6-IR cells were also present in sections of nodose ganglia. (C) 2002 Wiley-Liss, Inc.