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Voltage-dependence of contraction in streptozotocin-induced diabetic myocytes

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Abstract

Cardiac contractile dysfunction is frequently reported in human patients and experimental animals with type-1 diabetes mellitus. The aim of this study was to investigate the voltage-dependence of contraction in ventricular myocytes from the streptozotocin (STZ)-induced diabetic rat. STZ-induced diabetes was characterised by hyperglycaemia and hypoinsulinaemia. Other characteristics included reduced body and heart weight and raised blood osmolarity. Isolated ventricular myocytes were patched in whole cell, voltage-clamp mode after correcting for membrane capacitance and series resistance. From a holding membrane potential of −40 mV, test pulses were applied at potentials between −30 and +50 mV in 10 mV increments. L-type Ca2+ current (I Ca,L) density and contraction were measured simultaneously using a video-edge detection system. Membrane capacitance was not significantly altered between control and STZ-induced diabetic myocytes. The I Ca,L density was significantly (p < 0.05) reduced throughout voltage ranges (−10 mV to +10 mV) in myocytes from STZ-treated rats compared to age-matched controls. Moreover, the amplitude of contraction was significantly reduced (p < 0.05) in myocytes from STZ-treated rats at all test potentials between −20 mV and +30 mV. However, in electrically field-stimulated (1 Hz) myocytes, the amplitude of contraction was not altered by STZ-treatment. It is suggested that in field-stimulated myocytes taken from STZ-induced diabetic hearts, prolonged action potential duration may promote increased Ca2+ influx via the sodium-calcium exchanger (NCX), which may compensate for a reduction in Ca2+ trigger through L-type-Ca2+-channels and lead to normalised contraction. (Mol Cell Biochem 261: 235–243, 2004)

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Authors and Affiliations

  1. Department of Biological Sciences, University of Central Lancashire, Preston, England

    N.K. Bracken, A.J. Woodall & J. Singh

  2. Department of Physiology Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE

    F.C. Howarth

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  1. N.K. Bracken
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  2. A.J. Woodall
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  3. F.C. Howarth
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  4. J. Singh
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Bracken, N., Woodall, A., Howarth, F. et al. Voltage-dependence of contraction in streptozotocin-induced diabetic myocytes. Mol Cell Biochem 261, 235–243 (2004). https://doi.org/10.1023/B:MCBI.0000028761.61216.5e

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