Activation of ATP-sensitive K-channel promotes the anticonvulsant properties of cannabinoid receptor agonist through mitochondrial ATP level reduction

• Published in: Epilepsy & behavior 2019-04, Vol.93, p.1-6
• Main Authors: Haj-Mirzaian, Arvin, Ramezanzadeh, Kiana, Afshari, Khashayar, Mousapour, Pouria, Abbasi, Nooshin, Haj-Mirzaian, Arya, Nikbakhsh, Rajan, Haddadi, Nazgol-sadat, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: ATP level; Cannabinoid receptors; Clonic seizure threshold; Potassium channels
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2019.01.025

Cannabinoid receptor (CBR) agonist could act as a protective agent against seizure susceptibility in animal models of epilepsy. Studies have shown that potassium channels could play a key role in ameliorating neuronal excitability. In this study, we attempted to evaluate how CBRs and Adenosine Tri-Phosphate (ATP)-sensitive potassium channels collaborate to affect seizure susceptibility by changing the clonic seizure threshold (CST). We used male Naval Medical Research Institute (NMRI) mice and treated them with the following drugs: cromakalim (a potassium channel opener, 10 μg/kg), glibenclamide (a potassium channel blocker, 0.03 and 1 mg/kg), 0.5 mg/kg of AM-251 (a selective CB1 antagonist), AM-630 (a selective CB2 antagonist), and 0.5, 3, and 10 mg/kg of WIN 55,212-2 (a nonselective agonist of CBRs); and CST was appraised after each type of administration. Also, we evaluated the ATP level of the hippocampus in each treatment to clarify the interaction between the cannabinoid system and potassium channel. Our results showed that administration of WIN 55,212-2 at 10 mg/kg significantly increased CST (P