Altered diaphragm muscle action potentials in zucker diabetic fatty (ZDF) rats

The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes, being characterized by obesity, diabetes, and dyslipidemia. In vitro studies tested the hypothesis that diaphragm muscle from ZDF rats has abnormal resting membrane potential and action potentials, similar to type 1 diabetic rodents. Resting membrane potential was comparable for muscle from ZDF and control rats. Diaphragm from ZDF rats had augmented action potential peak height (92.1 mV versus 82.4 mV, P < 0.00001), overshoot (15.6 mV versus 8.1 mV, P < 0.001) and area (80.7 mV ms versus 68.6 mV ms, P < 0.001) compared with that from controls. Action potential rate of depolarization and repolarization were not affected. The K+ blocker, 3,4-diaminopyridine, augmented action potential duration and area of muscle from ZDF and controls, but without significant differences between animal groups. These findings in ZDF rats contrast with type 1 diabetic rats, suggesting that isolated hyperglycemia differs from hyperglycemia combined with other metabolic perturbations with respect to diaphragm electrophysiological derangements.