Diabetes, Vol 39, Issue 12 1485-1489, Copyright © 1990 by American Diabetes Association
Increased susceptibility to hypoxia of prolonged action potential duration in ventricular papillary muscles from diabetic rats
M Aomine, S Nobe and M Arita
Department of Physiology, Medical College of Oita, Japan.
The action potential duration (APD) of ventricular muscles obtained from
diabetic animals is reported to be prolonged. We studied the effect of
varied periods of diabetes on APD prolongation using isolated ventricular
papillary muscles from streptozocin-injected rats. We found that a diabetic
period greater than 30 wk was necessary for the evolution of significant
prolongation of APD. We then studied the effect of repeated hypoxia (PO2 40
mmHg) and normoxia (PO2 300 mmHg) on prolonged APD of diabetic muscles and
compared the findings with those from control rats. Transmembrane
potentials were recorded with conventional glass microelectrodes. Under
normoxic conditions, the APDs of diabetic muscles were significantly
prolonged, the maximum upstroke velocity of action potentials tended to be
decreased, and the resting membrane potential was not changed significantly
compared with controls. The first hypoxia (20 min) shortened the APD in
both diabetic and control rats but more so in diabetic rats, thereby making
the APD of diabetic rats virtually identical to the control rat APD during
the hypoxia. On subsequent reoxygenation (30 min), these hypoxia-induced
changes were almost recovered. The second hypoxia (20 min) produced more
severe shortening of the APD in both muscle types, and the effect was again
far greater in diabetic rats than controls, ending with a reversed sequence
of APDs and the APD of diabetic muscles much shorter than the controls.
Excessive shortening of APD in diabetic muscles during hypoxic conditions
was speculated to be due to greater increases in the outward K+ current
through ATP-regulated K+ channels that may be secondary to the more severe
reduction of intracellular ATP concentrations in diabetic versus control
hearts.