title: An isoprenaline activated sodium-dependent inward current in ventricular myocytes.
abstract: In the heart, catecholamines affect pacemaker activity by shifting the activation curve for the nonspecific inward current and increasing both the calcium current, and the delayed potassium current. We report here that in mammalian ventricle there is another mechanism that seems to involve a sodium-dependent inward current. This is elicited by agents that increase intracellular cyclic AMP concentration, such as the beta-adrenergic agonist isoprenaline, and is unaffected by agents which block the three currents listed above, but is absent when external sodium is replaced with tetramethylammonium. Most interestingly, the intracellular pathway(s) linking the beta-receptor(s) to activation of the Ca current and the Na-dependent current, which in both cases presumably involves the intracellular concentration of cAMP, differ, as isoprenaline causes a persistent augmentation of the calcium current whereas the Na-dependent current often fades. These effects of isoprenaline are antagonized by acetylcholine. In unclamped cells, the Na-dependent current depolarizes the membrane to the potential range at which repetitive firing occurs. It may therefore be involved in the generation of ventricular arrhythmias.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D007473:Ion Channels; D005576:Colforsin; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium