Effects of reducing [Na+]o on catecholamine-induced delayed afterdepolarizations in atrial cells

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+.