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Domoic Acid Attenuates the Adenosonine-5'- Triphosphate-Induced Increase in [Ca2+] i in Adult CardiomyocytesDepartment of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada Background: Although domoic acid (DA), a shellfish neurotoxin, carries a negative surface charge at physiological pH like that of adenosine-5'-triphosphate (ATP), very little is known about its cellular effects. In view of the potentially significant role of extracellular ATP as a signaling molecule for increasing the intracellular concentration of Ca2+ ([Ca2+]i), we examined the possibility that DA may interfere with this signal transduction mechanism in the myocardium. Methods and Results: Cardiomyocytes were isolated from rat heart and loaded with Fura-2 to measure the [Ca2+]i. ATP produced a gradual rise in [Ca2+]i, reaching a peak level in 25- 30 seconds and declining thereafter. DA did not affect the [Ca2+]i in cardiomyocytes; however, it diminished the ATP-induced elevation in [Ca2+]i in a concentration-dependent manner. Kainic acid, an analogue of DA, had a similar effect but at a 25-fold higher concentration, whereas glutamate and aspartate did not modify the action of ATP. Well-known inhibitors of L-type voltage-sensitive Ca2+ channels, nifedipine and nicardipine, depressed the ATP- induced increase in [Ca2+ ]i, but DA did not produce additive effects with either of these agents. On the other hand, DA potentiated the KCl-induced increase in [Ca2+]i in quiescent cardiomyocytes and augmented the nicardipine-sensitive Ca2+ transients in electrically stimulated cardiomyocytes. Conclusions: These results suggest that DA may diminish the ATP-induced increase in [Ca 2+]i by inhibiting the ATP interaction with cardiomyocytes in a specific manner.
Key Words: cardiomyocytes • domoic acid • Ca2+-homeostasis • ATP action.
Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 3,
159-165 (1999) |
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