Cardiac IKs as repolarization reserve plays a role in gender difference of diabetic QT prolongation

AIM: To explore the basic ionic mechanisms underlying long-QT syndrome by observing the changes of slowly activating outward rectifying potassium current (I_Ks) and its proteins in abnormal QT prolongation in different genders of diabetic rabbits.METHODS: A single injection of pre-warmed (37 ℃) alloxan (140 mg/kg) was used to establish a rabbit model of insulin-dependent diabetes mellitus. Eight weeks after alloxan injection, the levels of blood glucose in the rabbits were monitored and standard lead II electrocardiogram was recorded. The myocardial cells were isolated from the ventricle of the rabbits via enzymatic digestion. Whole-cell patch clamp technique was performed to study the action potential duration (APD) and I_Ks. The changes of both KvLQT1 and mink proteins were detected by Western blotting analysis.RESULTS: The QT interval and APD were prolonged apparently both in male and female diabetic rabbits. The increased APD/QT-I of the male diabetic rabbits is more remarkable than that of the female. The I_Ks step current density of the male diabetic rabbits was decreased at test potentials ranging from+40 mV to+70 mV compared with that of the control animals (P<0.05), which was lowered from (3.08±0.67) pA/pF (n=17) to (1.27±0.20) pA/pF (n=16) at+70 mV. However, the I_Ks step current density of the female diabetic rabbits was increased at test potentials ranging from 0 mV to+70 mV compared with that of control group (P<0.05), which was increased from (1.56±0.20) pA/pF (n=13) to (3.65±0.50) pA/PF (n=14) at+70 mV. The expression of KvLQT1 and mink in male diabetic group decreased by 21.6% and 18.5%, respectively. However, the expression of KvLQT1 and mink in female diabetic group were increased by 42.3% and 20.5%, respectively.CONCLUSION: The I_Ks may be a protective factor in the early period of diabetic development in female rabbits. As a repolarization reserve, cardiac I_Ks is likely to restrict the effects of excessively slowing repolarization.