[Experimental approaches to determining molecular mechanisms of antiarrhythmic and cardioprotective actions of new compounds].
The comparative study of ion homeostatic regulation in the cardiomyocytes in health and in experimental hypoxia showed that the elevated diastolic concentration of free ions of sodium ([Na+]in and calcium ([Ca2+]cyt) in the cardiomyocytic cytoplasm, the lower resting potential of the cell plasma membrane (delta phi n) are major arrhythmogenic agents. The decreased (delta phi n) is mainly defined by lower Na+/K(+)-ATPase activity due to insufficient energy production. The activation of Na+/H(+)-antiport underlies the elevation of [Na+]cyt. The mechanisms responsible for increased [Ca2+]cyt are increased Na/Ca exchange and inhibited Ca-ATPases in the sarcoplasmic reticulum. A test system was developed to choose and study the antiarrhythmic activity of new agents in in vitro experiments by using isolated cardiomyocytes. The screening scheme proposed involves a consecutive evaluation of the effects of chemicals on the changes occurring in the (delta phi n) of cellular Na and Ca exchange. A concept describing the molecular and cellular factors predisposing to cardiac arrhythmias and ischemic alteration is formulated; possible points of application of the cardioprotective and antiarrhythmic agents were identified.
Dukhanin
A S
AS
Khankoeva
A I
AI
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004338:Drug Combinations; D006801:Humans; D016623:Ion Pumps / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
D000889:Anti-Arrhythmia Agents; D002317:Cardiovascular Agents; D004338:Drug Combinations; D016623:Ion Pumps