HYPOTONICALLY INDUCED CALCIUM INCREASE AND REGULATORY VOLUME DECREASEIN NEWBORN RAT CARDIOMYOCYTES

The effect of cell swelling on intracellular calcium concentration ([C a2+](i)) was studied in newborn rat cardiomyocytes. Hypotonic cell swe lling induced a fast and transient [Ca2+](i) increase (hypotonically i nduced calcium increase, HICI; 388+/-47 nM, n=14). HICI was not inhibi ted by cyclopiazonic acid (CPA), an inhibitor of sarcoplasmic Ca2+-ATP ase, nor ryanodine (an inhibitor of calcium-induced calcium release), whereas it was abolished (11+/-19 nM, n=5) in the absence of external calcium. Thus, HICI appeared to depend exclusively on entry of externa l calcium. Gadolinium ion (Gd3+), a generic inhibitor of stretch-activ ated cation channels (SACs), was unable to affect HICI (353+/-79 nM, n =6). Similarly, HICI was unaffected by internal Naf depletion and exte rnal Na+ omission. These results suggest that neither Gd3+-sensitive S ACs nor Na+-Ca2+ exchange is responsible for HICI. Conversely, HICI wa s inhibited by diltiazem (42+/-4 nM, n=3) and by membrane predepolariz ation (40+/-18 nM, n=5), suggesting an involvement of L-type voltage-a ctivated calcium channels. Cardiomyocyte swelling was followed by a re gulatory volume decrease (RVD). The putative role of HICI in volume re gulation was studied by removal of external calcium. This procedure si gnificantly slowed RVD but did not abolish it. In conclusion, newborn rat cardiomyocytes exhibit an external-calcium-dependent HICI which co ntributes partially to the RVD.