Peptidergic innervation of human atrial myocardium: an electron microscopical and immunocytochemical study

Nerve terminals of human cardiac muscle were studied using an electron microscope. Substance P-, Leu-enkephalin- and vasoactive intestinal polypeptide-like (VIP) immunoreactive nerves were demonstrated by use of the light microscope. In addition, VIP- and substance P-like immunoreactive nerves were localized ultrastructurally by the peroxidase-antiperoxidase-method. Muscle specimens were obtained from right auricula of patients undergoing open-heart surgery. In the nerve fibres and terminals, which were situated close to the blood vessels and cardiac muscle cells several vesicle populations were identified. On the morphological basis the terminals could be tentatively categorized as cholinergic, mixed cholinergic-peptidergic, adrenergic, sensory or baroreceptor type, peptidergic and degenerating nerve endings. Substance P-, Leu-enkephalin- and VIP-like immunoreactive nerves were localized between cardiac muscle cells. Nerve terminals, which showed substance P-immunoreaction were observed also close to blood vessels. In substance P- and VIP-immunoreactive nerve terminals the immunoprecipitation was localized in large dense-cored vesicles of about 120 nm in diameter. It is concluded that the intrinsic control of the human heart is most probably regulated by several transmitter candidates. The peptidergic nerves may exert their modulatory interactions in the nerve bundles where they are situated close to each other but a direct effect on the blood vessels and muscle cells cannot be excluded.