Effects of Chan Su, a traditional Chinese medicine, on the calcium transients of isolated cardiomyocytes: cardiotoxicity due to more than Na, K-ATPase blocking.
Extracts of Chan Su, a traditional Chinese medication used as a topical anesthetic and cardiac medication, were incubated with cardiomyocytes that had been loaded with a calcium specific fluorescent probe. Calcium transients were measured by real-time fluorescence spectrophotometry following treatment. The transients were rapidly abolished following addition of a moderate concentration of the extract (400 ng/ml), resulting in high levels of intracellular calcium, while the lower amount (40 ng/ml) blocked the sodium-potassium adenosine triphosphatase. Treatments with ouabain and nifedipine were also made, either prior to, or after the addition of the Chan Su, in an attempt to better delineate the site(s) of action. The moderate concentration of Chan Su (400 ng/ml) extract caused the myocytes to cease beating within seconds of addition, even in experiments when saturating concentrations of nifedipine or ouabain had been previously added to the cells. As expected bufalin, the active component of Chan Su has similar effects. Our findings indicate that this compound is extremely cardiotoxic, even in small dose and acts rapidly to alter intracellular calcium stores in cardiomyocytes and possibly acts at sites other than the Na(+)+K(+) ATPase, either directly, or indirectly via changes in calcium concentrations.
Bick
Roger J
RJ
Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, 6431 Fannin Street, 77030, USA.
Poindexter
Brian J
BJ
Sweney
Roxanne R
RR
Dasgupta
Amitava
A
D000664:Amphibian Venoms / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D002018:Bufanolides / Q000494:pharmacology / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000633:toxicity; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D008516:Medicine, Chinese Traditional; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000664:Amphibian Venoms; D002018:Bufanolides; D002316:Cardiotonic Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; C095591:chan su; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D002118:Calcium; C022777:bufalin