Voltage-dependence of contraction in streptozotocin-induced diabetic myocytes

• Published in: Molecular and cellular biochemistry 2004-06, Vol.261 (1-2), p.235-243
• Main Authors: Bracken, N K, Woodall, A J, Howarth, F C, Singh, J
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calcium Channels, L-Type - physiology; Diabetes; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - physiopathology; Heart Ventricles - physiopathology; Male; Myocardial Contraction - physiology; Myocytes, Cardiac - physiology; Rats; Rats, Wistar; Rodents; Sodium-Calcium Exchanger - physiology
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/B:MCBI.0000028761.61216.5e

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.