Decrease in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes

This study was designed in order to gain insight into possible changes in t he inward sodium-calcium exchange current (INa-Ca) and the L-type calcium c urrent (I-Ca), in ventricular myocytes isolated from streptozotocin-induced diabetic rats. Recordings were made using the nystatin-perforated patch te chnique which minimizes interference with the normal intracellular Ca2+ buf fering mechanisms. The averaged ka-ca current density elicited by Ca2+ curr ent was smaller in diabetic than in normal myocytes at all potentials teste d. INa-Ca activated by rapid application of caffeine was significantly redu ced and the decay phase was prolonged. The density of lc, was also signific antly reduced by diabetes in the range of rest potentials between -10 and 50 mV. In addition, the fast time constant of Ic, inactivation, which repre sents mainly the sarcoplasmic reticulum (SR) Ca2+ release-induced inactivat ion, was significantly higher in diabetic than in normal myocytes. The decr ease in I-Ca, which is the main source of trigger Ca2+ for SR Ca2+ release, may explain the significantly lowered peak systolic [Ca2+](i) previously s hown in diabetic myocytes. As activation of lc, is essential Tor subsequent stimulation of INa-Ca, reduced I-Ca may contribute to decreasing activatio n of the Na+-Ca2+ exchanger.