[Role of ATP-sensitive potassium channels in the clonic seizure threshold induced by pentylenetetrazole in mice with diabetes type I]

ABSTRACT

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. On the other hand, several studies have suggested a pivotal role for K[ATP] channels in the seizure modulation. So, the present study was designed to evaluate the seizure threshold induced by pentylenetetrazole [PTZ] in diabetic mice at different times and to examine the possible role of ATP-sensitive potassium [K[ATP]] channels. In this experimental study, NMRI were diabetic with streptozocine. Then clonic seizure thresholds were determined at different times after induction of diabetes compared with corresponding non-diabetic groups. Each experimental group consisted of ten mice. There was a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after STZ injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The non-effective dose of K[ATP] channel blocker glibenclamide [1 mg/kg, i.p.], but not the voltage-dependent K+ channel blocker 4-aminopyridine [1 mg/kg, i.p.], decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with the K[ATP] channel opener cromakalim [10 micro g/kg, i.p.]. Moreover, the non-effective dose of cromakalim [10 micro g/kg, i.p.] increased significantly the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide [1 mg/kg, i.p.] but not with 4-aminopyridine [1 mg/kg, i.p.]. This study indicated that the PTZ-induced seizure threshold is altered in diabetic mice in a time-dependent manner which could be due to the probable alteration in the K[ATP] channel functioning during diabetes