Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 44
Energy failure
ОглавлениеSustained neuronal activation also markedly increases energy, namely ATP, utilization to restore ion gradients across the membrane. In some neurons, the presence of an ATP-gated potassium channel (KATP) reduces neuronal activity when ATP levels decline intracellularly (Yamada et al., 2001). When the ATP level falls because energy utilization outpaces energy production, potassium channels open and produce membrane hyperpolarization. Indeed, knockout mice lacking functioning KATP channels experience a myoclonic seizure on average 8.9 ± 1.1 s following onset of hypoxia, followed by generalized convulsions and death. A similar hypoxic challenge, however, does not trigger seizures in wild-type mice, indicating that KATP channels in vivo resist membrane depolarization during energy failure. Reduced levels of energy metabolites, such as glucose, may also affect seizure duration. In vitro recordings show that decreasing extracellular glucose terminates electrographic seizure-like activity in the low magnesium hippocampal slice (Kirchner et al., 2006). The effect of hypoglycaemia on seizure-like discharges in vitro was statistically significant, but not immediate. Fifty per cent fewer seizure-like discharges occurred in the 24-min period following application of low glucose artificial cerebrospinal fluid compared to the frequency of discharges in the 30 min prior to application. Low glucose also reduced the amplitude of the seizure-like discharge by 25%. These effects on the frequency and amplitude of seizure-like discharges were reversed by restoration of normal glucose levels.