TY - GEN
T1 - Effects of streptozotocin-induced diabetes on contraction and calcium transport in rat ventricular cardiomyocytes
AU - Bracken, Nicholas
AU - Howarth, Frank C.
AU - Singh, Jaipaul
PY - 2006/11
Y1 - 2006/11
N2 - Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)-induced type 1 DMon contraction, L-type calcium (Ca2+) current (ICa2+L), and on cytosolic calcium concentrations [Ca2+]i in ventricular myocytes of the rat heart. After 4-10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age-matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of ICa2+L and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range -10 mV to +20 mV and -30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age-matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine-evoked time to half relaxation of the Ca2+ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl2). It is concluded that the diabetes-induced voltage-dependent decrease in contraction is associated with reduced Ca2+ channel activities and prolonged diastolic cytosolic Ca2+ compared to age-matched control. Taken together, the results suggest that Ca2+ homeostasis is deranged during DM and this may be expressed at the level of the Na+/Ca 2+ exchanger.
AB - Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients. Contractile function of the heart is frequently compromised in the clinical setting and in experimental models of diabetes mellitus (DM). This article investigated the effect of streptozotocin (STZ)-induced type 1 DMon contraction, L-type calcium (Ca2+) current (ICa2+L), and on cytosolic calcium concentrations [Ca2+]i in ventricular myocytes of the rat heart. After 4-10 weeks of STZ treatment, blood glucose levels in diabetic animals were significantly (P < 0.05) higher compared to age-matched controls. Diabetic rats have significantly (P < 0.05) reduced body, reduced heart weight, and reduced viability of ventricular myocytes compared to controls. The amplitude of ICa2+L and amplitude of contraction were significantly reduced (P < 0.05) at test potentials in the range -10 mV to +20 mV and -30 mV to +40 mV, respectively, in myocytes from diabetic animals compared to age-matched controls. Moreover, there was a significant (P < 0.05) delay in electrically stimulated and caffeine-evoked time to half relaxation of the Ca2+ transient in myocytes from diabetic animals compared to controls. A similar effect was obtained in myocytes treated with a combination of caffeine and nickel chloride (NiCl2). It is concluded that the diabetes-induced voltage-dependent decrease in contraction is associated with reduced Ca2+ channel activities and prolonged diastolic cytosolic Ca2+ compared to age-matched control. Taken together, the results suggest that Ca2+ homeostasis is deranged during DM and this may be expressed at the level of the Na+/Ca 2+ exchanger.
KW - Calcium
KW - Contraction
KW - Diabetes
KW - Heart
KW - Rat
KW - Streptozotocin
KW - Ventricular myocytes
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U2 - 10.1196/annals.1372.018
DO - 10.1196/annals.1372.018
M3 - Conference contribution
C2 - 17151303
AN - SCOPUS:34447626824
SN - 1573316350
SN - 9781573316354
T3 - Annals of the New York Academy of Sciences
SP - 208
EP - 222
BT - Diabetes Mellitus and Its Complications
PB - Blackwell Publishing Inc.
ER -
