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 (ICa,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 ICa,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.
Original language | English |
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Pages (from-to) | 235-243 |
Number of pages | 9 |
Journal | Molecular and cellular biochemistry |
Volume | 261 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jun 2004 |
Keywords
- Calcium current
- Diabetes
- Heart
- Streptozotocin
- Ventricular myocytes
- Voltage-dependence of contraction
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology