AIMS: We have recently reported that amiloride, a potent and nonselective blocker of acid-sensing ion channels, prevents the development of pilocarpine-induced seizures and status epilepticus. Amiloride is also known to suppress the activity of Na(+) /Ca(2+) and Na(+) /H(+) exchangers that have been implicated in the pathophysiology of seizures. Here, we evaluated the effects of amiloride, SN-6 (a potent blocker of Na(+) /Ca(2+) exchangers) and zoniporide (a potent blocker of Na(+) /H(+) exchangers) on acoustically evoked seizures (audiogenic seizures, AGS) in genetically epilepsy-prone rats (GEPR-3s), a model of inherited generalized epilepsy. METHODS: Male, six-week-old GEPR-3s were used. The GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of amiloride, SN-6, and zoniporide (1, 3, 10, and 30 mg/kg; per os). RESULTS: We found that pretreatment with amiloride and SN-6 markedly reduced the incidence and severity of AGS in the GEPR-3s. In contrast, administration of zoniporide only minimally reduced the incidence and severity of AGS in the GEPR-3s. A combination of noneffective doses of SN-6 and zoniporide also suppressed AGS susceptibility in the GEPR-3s. CONCLUSIONS: These findings suggest acid-sensing ion channels and the Na(+) /Ca(2+) exchanger may play an important role in the pathophysiology of inherited AGS susceptibility in the GEPR-3s.
AIMS: We have recently reported that amiloride, a potent and nonselective blocker of acid-sensing ion channels, prevents the development of pilocarpine-induced seizures and status epilepticus. Amiloride is also known to suppress the activity of Na(+) /Ca(2+) and Na(+) /H(+) exchangers that have been implicated in the pathophysiology of seizures. Here, we evaluated the effects of amiloride, SN-6 (a potent blocker of Na(+) /Ca(2+) exchangers) and zoniporide (a potent blocker of Na(+) /H(+) exchangers) on acoustically evoked seizures (audiogenic seizures, AGS) in genetically epilepsy-prone rats (GEPR-3s), a model of inherited generalized epilepsy. METHODS: Male, six-week-old GEPR-3s were used. The GEPR-3s were tested for AGS susceptibility before and after treatment with various doses of amiloride, SN-6, and zoniporide (1, 3, 10, and 30 mg/kg; per os). RESULTS: We found that pretreatment with amiloride and SN-6 markedly reduced the incidence and severity of AGS in the GEPR-3s. In contrast, administration of zoniporide only minimally reduced the incidence and severity of AGS in the GEPR-3s. A combination of noneffective doses of SN-6 and zoniporide also suppressed AGS susceptibility in the GEPR-3s. CONCLUSIONS: These findings suggest acid-sensing ion channels and the Na(+) /Ca(2+) exchanger may play an important role in the pathophysiology of inherited AGS susceptibility in the GEPR-3s.
Authors: G A Cox; C M Lutz; C L Yang; D Biemesderfer; R T Bronson; A Fu; P S Aronson; J L Noebels; W N Frankel Journal: Cell Date: 1997-10-03 Impact factor: 41.582
Authors: Ravi B Marala; Janice A Brown; Jimmy X Kong; W Ross Tracey; Delvin R Knight; Ronald T Wester; Dexue Sun; Scott P Kennedy; Ernest S Hamanaka; Roger B Ruggeri; Roger J Hill Journal: Eur J Pharmacol Date: 2002-09-06 Impact factor: 4.432