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Role of ATP-sensitive potassium channels in the clonic seizure threshold inuced by pentylenetetrazole in mice with diabetes type I
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Hamed Shafaroodi1   , Mehrdad Hashemi , Ahmad Reza Dehpour |
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Abstract: (22212 Views) |
Background: 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 KATP 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 (KATP) channels.
Materials and methods: 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.
Results: 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 KATP 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 KATP channel opener cromakalim (10 μg/kg,i.p.). Moreover, the non-effective dose of cromakalim (10 μg/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.).
Conclusion: 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 KATP channel functioning during diabetes. |
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| Keywords: Diabetes, Clonic seizure threshold, ATP-sensitive potassium (KATP) channel, Glibenclamide, Cromakalim, Mice |
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Full-Text [PDF 1032 kb]
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Subject:
Epidemiology
Received: 2010/08/19 | Published: 2010/04/15
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