Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition.
To investigate the role of Ca2+ metabolism and pH in diabetic cardiomyopathy, intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) of isolated myocytes were measured simultaneously using fura-2 and BCECF. We used diabetic (D.M.) rats at 8 weeks after the injection of streptozotocin (45 mg/kg, i.v.). (1) [Ca2+]i of D.M. myocytes was lower than that of controls (53 +/- 3 and 75 +/- 5 nM, mean +/- S.E., P less than 0.01). There was no difference in pHi (7.06 +/- 0.02 in D. M., 7.07 +/- 0.02 in control). There was no difference in the percentage of non-rounded cells at 30 min after the perfusion of glucose-free solution which contained 2 mM sodium cyanide (NaCN) between D.M. and controls (53% and 52%). When cells were rounded, the value of [Ca2+]i was significantly lower in D.M. myocytes than that in controls (172 +/- 21 and 421 +/- 106 nM, P less than 0.05). (2) When the cells were shortened or rounded in the high [Ca2+]o solution (24.5 mM), [Ca2+]i of D.M. rats was significantly lower than that of control rats. (3) The percentage of non-rounded cells at 30 min after the perfusion of NaCN increased in controls by 50 mM glucose (95%, P less than 0.01), but not in D.M. (47%). Insulin (25 mU/ml) and glucose (15 mM) increased the percentage of non-rounded cells in D.M. after 30 min perfusion with NaCN (88%, P less than 0.01 v.s. 53% without glucose nor insulin). It is suggested that there are disturbances of Ca2+ metabolism in D.M. myocytes, and that there is a close relation between cell injury and glucose utilization during metabolic inhibition.
Noda
N
N
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Hayashi
H
H
Miyata
H
H
Suzuki
S
S
Kobayashi
A
A
Yamazaki
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000494:pharmacology*
D007328:Insulin; D005947:Glucose; D012966:Sodium Cyanide; D002118:Calcium