kappa-Opioid receptor stimulation increases intracellular free calcium in isolated rat ventricular myocytes

The effect of two specific kappa-agonists, dynorphinA1-13 and U50,488H, on intracellular free calcium [Ca]i in isolated rat ventricular myocytes was studied. A spectrofluorimetric method using fura 2 as calcium indicator was employed. It was found that both agonists increased [Ca]i dose-dependently. The effect was attenuated by Mr 2266, a kappa-antagonist, indicating that the effect is a kappa-receptor mediated event. The effect was abolished by pretreatment with ryanodine, a drug that mobilizes calcium from the sarcoplasmic reticulum. It was, however, not affected by nifedipine, a calcium antagonist or removal of external calcium. The results indicate that the increase in [Ca]i due to kappa-opioid receptor stimulation results primarily from mobilization of calcium from an intracellular pool.