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 the inward sodium-calcium exchange current (INa-Ca) and the L-type calcium current (ICa), in ventricular myocytes isolated from streptozotocin-induced diabetic rats. Recordings were made using the nystatin-perforated patch technique which minimizes interference with the normal intracellular Ca2+ buffering mechanisms. The averaged INa-Ca current density elicited by Ca2+ current was smaller in diabetic than in normal myocytes at all potentials tested. INa-Ca activated by rapid application of caffeine was significantly reduced and the decay phase was prolonged. The density of ICa was also significantly reduced by diabetes in the range of test potentials between -10 and +50 mV. In addition, the fast time constant of ICa inactivation, which represents mainly the sarcoplasmic reticulum (SR) Ca2+ release-induced inactivation, was significantly higher in diabetic than in normal myocytes. The decrease in ICa, which is the main source of trigger Ca2+ for SR Ca2+ release, may explain the significantly lowered peak systolic [Ca2+]i previously shown in diabetic myocytes. As activation of ICa is essential for subsequent stimulation of INa-Ca, reduced ICa may contribute to decreasing activation of the Na+-Ca2+ exchanger.
Chattou
S
S
Laboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France.
Diacono
J
J
Feuvray
D
D
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002412:Cations / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D013311:Streptozocin
D015220:Calcium Channels; D002412:Cations; D013311:Streptozocin; D012964:Sodium; D002118:Calcium