Adrenergic-cholinergic interaction that modulates repolarization in the atrium is altered with aging.
BACKGROUND
Aging is associated with involution of both limbs of the autonomic nervous system, and the prejunctional and postjunctional effects of adrenergic and cholinergic stimulation are altered with senescence. Hence, postjunctional age-related changes in adrenergic-cholinergic interaction are a likely occurrence and may contribute to an altered substrate for arrhythmias.


RESULTS
Microelectrode techniques were used to record action potentials from epicardial slices of Bachmann's bundles of dogs aged 3 to 5 years (adult) and 8 to 12 years (old) in the absence or presence of acetylcholine and isoproterenol (separately and in combination). In control, action potential duration to 90% repolarization (APD) was longer in old atria. Acetylcholine (10(-8) to 10(-5) mol/L) in a concentration-dependent manner hyperpolarized and shortened APD in both tissues, with more prominent effects in the old. The effects of isoproterenol (10(-9) to 10(-6) mol/L) to elevate the plateau and shorten APD were about the same in both adult and old tissues. In adults, low concentrations of isoproterenol (10(-9) and 10(-8) mol/L) significantly prolonged APD, which had been first shortened by acetylcholine. This effect of isoproterenol was decreased in old atrial tissue, resulting in shorter APD in old than adult atria in the combined presence of beta-adrenergic and muscarinic agonists.


CONCLUSIONS
In adult Bachmann's bundle, beta-adrenergic stimulation effectively operates as a "brake" to decrease the extent of cholinergic-induced APD shortening. The action of beta-adrenergic stimulation to antagonize acetylcholine-induced acceleration of repolarization declines with age, which may contribute to an altered arrhythmogenic substrate.
Sosunov
Eugene A
EA
Center for Molecular Therapeutics, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Anyukhovsky
Evgeny P
EP
Rosen
Michael R
MR
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D014665:Vasodilator Agents; D007545:Isoproterenol; D000109:Acetylcholine