A hypothesis for cyanide-induced tonic seizures with supporting evidence

A possible relationship among cyanide-induced convulsions, calmodulin, nitric oxide and protein kinase C was investigated in mice. The ED50 value of cyanide as measured by induction of tonic seizures was significantly increased in a dose-dependent manner when mercuric chloride (0.5 or 5.0 nmol/body), gangliosides (GGS) (90 nmol/body), a protein kinase C inhibitor or trifluoperazine (TFP) (45 or 90 nmol/body), a calmodulin inhibitor were preinjected intracerebroventricularly (i.v.t.) and NG-nitro-L-arginine (NNA) (300 mg/kg), a nitric oxide (NO) synthase inhibitor was preinjected intraperitoneally (i.p.) in mice. These results suggest that protein kinase C, calmodulin, and NO dependent cyclic guanosine monophosphate (GMP) dependent enzymes may contribute to the induction of convulsions. In contrast, 2,4-dinitrophenol (DNP) (50 nmol/body, intracerebroventricularly (i.v.t.), an uncoupler of oxidative phosphorylation significantly decreased the ED50 value of cyanide. In addition, DNP (100 nmol/body, i.v.t.) produced a severe tonic seizure in all of the treated mice. These indicate that adenosine triphosphate (ATP) depletion may also contribute in part to the development of cyanide-induced convulsions.