Drugs affecting the calcium-dependent slow depolarization mechanism of the cardiac cell membrane.
Transmembrane action potentials were recorded from isolated electrically paced cat and guinea pig left auricles in Tyrode solution and in the presence of 25 mM K+ or tetrodotoxin (TTX). The overshoot (OS) was increased, and the plateau of the action potential (AP) was shortened by epinephrine (5 X 10(-6)M) and by celluline-A (an organic calcium complex obtained from frog skin). The maximum rate of depolarization (Vmax) was enhanced by serotonin (5-HT) (10(-6)M), prostaglandin F2 alpha (2.8 X 10(-6)M), and by celluline-A. After inactivation of the fast sodium channel by TTX (10(-5)M) or by partial depolarization (25 mM K+ Tyrode) of electrically driven cat and guinea pig left auricle, catecholamines (epinephrine and isoproterenol, 4 X 10(-7) to 5 X 10(-6)M), histamine (10(-6) to 10(-5)M), and celluline-A restored the electrical and mechanical activity. Prostaglandins (PGE1, PGF2 alpha, 1.4 X 10(-8)-2.8 X 10(-6)M), 5-HT (10(-6)-5 X 10(-6)M), and 4-aminopyridine (1.5 X 10(-4)M) were ineffective in such conditions. The beta-adrenergic blocking agent pindolol (4 X 10(-7)M) prevented only the effect of catecholamines; the H1 receptor blocker mepyramine (10(-5)M) antagonized only that of histamine, and D-600 (2 X 10(-6)M), a selective Ca channel blocker, prevented the restoring effect of catecholamines, histamine, and celluline-A.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000494:pharmacology; D002415:Cats; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014020:Tissue Extracts / Q000494:pharmacology
D000631:Aminopyridines; D002395:Catecholamines; D007473:Ion Channels; D011453:Prostaglandins; D014020:Tissue Extracts; D012701:Serotonin; C006940:celluline A; D013779:Tetrodotoxin; D006632:Histamine; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium