Chronotropic Responsiveness of Developing Sinoatrial and Ventricular Rat Myocytes to Autonomic Agonists Following Adrenergic and Cholinergic Innervation In Vitro

• Published in: Circulation research 1989-06, Vol.64 (6), p.1051-1062
• Main Authors: Atkins, Dianne L, Marvin, William J
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Animals, Newborn; Biological and medical sciences; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Heart - drug effects; Heart - innervation; Isoproterenol - pharmacology; Myocardial Contraction; Myocardium - cytology; Norepinephrine - pharmacology; Parasympathetic Nervous System - physiology; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Rats; Rats, Inbred WKY; Sinoatrial Node - cytology; Sinoatrial Node - drug effects; Sinoatrial Node - innervation; Sympathetic Nervous System - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.64.6.1051

The chronotropic responses of isolated sinoatrial node and ventricular muscle cells to neurotransmitters were compared in vitro with and without selective adrenergic and cholinergic innervation. Explants of either thoracolumbar sympathetic ganglion or sacrococcygeal spinal cord were added to cultures of newborn rat sinus node regions or ventricular apexes harvested before the onset of autonomic innervation in vivo. Catecholamine synthesis was detected by glyoxylic acid histofluorescence. Acetylcholine synthesis was indicated by monoclonal antibody labeling of choline acetyltransferase. After electrical or pharmacological stimulation of neurons, the chronotropic response of individual myocardial cells confirmed the presence of neuroeffector transmission; the nature of the myocyte response identified the stimulated neuron as either adrenergic or cholinergic. Chronotropic responses of all myocardial cells to norepinephrine or acetylcholine were transcribed on a recorder coupled to a video photoconductive cell monitor. Isolated sinoatrial node cells were supersensitive to norepinephrine and acetylcholine; thresholds were 3xl0M and 6xlOM, respectively. These sinoatrial node cells remained sensitive to both norepinephrine and acetylcholine after the development of innervation in vitro. Ventricular cells also were sensitive with thresholds of 3xlO M and 6xl0 M to noreprinephrine and acetylcholine, respectively. However, following in vitro innervation, ventricular cells were significantly less sensitive to noreprinephrine and acetylcholine (thresholds 3x10 M and 6x10 M). These data are the first to demonstrate that neurotrophic modulation is not homogeneous throughout the myocardium and that it may be dependent on the specific myocardial cell innervated.