title: Effects of reducing [Na+]o on catecholamine-induced delayed afterdepolarizations in atrial cells.
abstract: Atrial cells of the canine coronary sinus generate arrhythmogenic delayed afterdepolarizations (DADs) in the presence of catecholamines. We studied the direct effects of reducing extracellular Na+ concentration ([Na+]o) to determine whether it is an important charge carrier of the DADs. We also compared the effects of sucrose substitution and Li+ substitution to obtain some insight into the ionic mechanism mediating the DADs, because Li+ can substitute for Na+ in various Na+ channels but not in electrogenic Na+-Ca2+ exchange. Reducing [Na+]o for 2-5 min caused complicated changes in electrical and mechanical properties of coronary sinus cells. When Li+ was used as a substitute, there was initially a decrease in the DAD within 25 s. Action potential duration decreased, resting tension increased, and twitch tension decreased. After 85 s, a small delayed afterdepolarization reappeared, membrane potential depolarized, and the aftercontraction increased. When sucrose was used as a substitute similar changes occurred except membrane potential hyperpolarized. Some of these changes suggest an elevation in intracellular [Ca2+] and subsequent alterations in membrane properties. To distinguish the direct effect of reducing [Na+]o from these indirect effects, we used a fast-flow superfusion system and thin, small preparations (approximately 1 mm wide, 4 mm long, and 6-12 cell layers thick). Under such conditions, 2- to 3-s solution changes could modify extracellular [Na+] without significantly affecting intracellular ionic composition. Brief periods of [Na+]o reduction during the DAD caused a decrease in its amplitude and rate of depolarization when either sucrose or Li+ was used as a substitute for Na+, without the other changes in membrane potential which occur during prolonged [Na+]o reduction. These results suggest Na+ is an important charge carrier for the inward current causing DADs in coronary sinus cells, and the membrane system mediating DADs may be either electrogenic Na+-Ca2+ exchange or a combination of electrogenic Na+-Ca2+ exchange and some other mechanism such as cation channels permeable to Li+.
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D007477:Ions; D008094:Lithium / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology; D009994:Osmolar Concentration; D012964:Sodium / Q000494:pharmacology*; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors
chemical_list: D002395:Catecholamines; D007477:Ions; D013395:Sucrose; D008094:Lithium; D012964:Sodium