Regional distribution and extrinsic innervation of intrinsic cardiac neurons in the guinea pig

Mammalian intrinsic cardiac neurons subserve different functions in differe nt cardiac regions, but the regional anatomical organisation of the intraca rdiac nervous system is not well understood. We investigated the quantitati ve and qualitative distribution of cholinergic and adrenergic elements, and the intracardiac pathways of extrinsic cardiac nerves, in whole-mount prep arations of guinea pig atria. Protein gene product 9.5 immunoreactivity (PG P 9.5-IR) marked intracardiac neuronal elements; immunoreactions for cholin e acetyltransferase (ChAT-IR) and tyrosine hydroxylase (TH-IR) distinguishe d cholinergic and adrenergic components, respectively. Catecholamine-contai ning components were identified by aldehyde-induced fluorescence histochemi stry. Mean total number of atrial neurons was 1510 +/- 251 (SE); 85% of the se occurred in ganglia of less than or equal to 20 neurons. All neuronal so mata expressing PGP 9.5-IR also expressed ChAT-IR, suggesting that these ne urons were cholinergic. Right (RA) and left (LA) atria had statistically si milar neuronal densities (6.4 +/- 1.2 and 2.4 +/- 0.7 neurons/mm(2), respec tively; analysis of variance, P less than or equal to 0.05). Neurons in RA were concentrated intercavally; LA neurons were concentrated near pulmonary vein ostia. Greatest density occurred in the interatrial septum (16.3 +/- 4.0 neurons/mm(2)). No neuronal somata expressed TH-IR or contained detecta ble amines but these elements were expressed by somata of small cells (mean total 124 +/- 33) throughout the atria, primarily associated with ganglia. Amine- and TH- containing varicosities were also present in ganglia, repre senting potential sites for adrenergic modulation of ganglionic neurotransm ission. Branches of extrinsic cardiopulmonary and vagus nerves were distrib uted to all parts of both atria. The organisation of the intracardiac nervo us system revealed in this study will facilitate further investigations of regional autonomic control of the heart. J. Comp. Neurol. 407:303-317, 1999 . (C) 1999 Wiley-Liss, Inc.