Drugs affecting the tetrodotoxin-sensitive ("fast") sodium mechanism in the cardiac cell membrane.
Prostacyclin, a newer member of the prostaglandin family, has been shown to stimulate the fast sodium system in the heart. A stimulatory effect of celluline-A, a biological Ca complex obtained from frog skin, has been demonstrated on both the fast and slow depolarization mechanisms. Prostacyclin and celluline-A are capable of restoring the electrical excitability of the isolated cat auricle poisoned with 3.5 mM MnCl2, i.e., in a situation when epinephrine is ineffective. We conclude that the normal cardiac cell membrane is tuned in such a way that the contribution of both the fast and slow depolarization mechanisms is necessary to generate an action potential, which is the result of their synergistic action. But both of them have remarkable reserve capacity which can be mobilized by their respective stimulators. With this reserve capacity mobilized, either of the two mechanisms can generate an action potential on its own, without the contribution of the other. Epinephrine can mobilize the reserve capacity of the slow mechanism, and prostacyclin that of the fast one. Celluline-A is a potent stimulator of both depolarization mechanisms.
D000818:Animals; D002415:Cats; D002712:Chlorides; D004558:Electric Stimulation; D004562:Electrocardiography; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D009200:Myocardial Contraction / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014020:Tissue Extracts / Q000494:pharmacology
D002712:Chlorides; D007473:Ion Channels; D017895:Manganese Compounds; D011453:Prostaglandins; D014020:Tissue Extracts; C006940:celluline A; D008345:Manganese; D013779:Tetrodotoxin; D012964:Sodium; D011464:Epoprostenol; C025340:manganese chloride; D004837:Epinephrine