K0ATP Expression Affects Seizure Susceptibility

Hypoglycemic seizures occur in several diseases, particularly diabetes. In rats (and humans) seizures are induced by excess insulin, which stimulates glucose uptake throughout the body, reducing the amount available to neurons. The substantia nigra pars reticulata (SNR) has been implicated in seizure control: hyperpolarization of SNR neurons is anticonvulsant, whereas increased firing in SNR is proconvulsant. To further investigate the mechanism of hypoglycemic seizures, Velíšek et al. injected insulin into rats that had fasted overnight. Fasting doubled the probability that insulin would induce a seizure and decreased the latency to seizure. But differences in blood glucose levels did not explain the difference. Instead, the proconvulsant effect of fasting was associated with decreased expression of K_ATP channels specifically in the SNR. These channels normally open (causing hyperpolarization) only when ATP levels are low (e.g., during hypoglycemia). Decreased K_ATP expression prevents hyperpolarization of SNR neurons during hypoglycemia, and thus is proconvulsant.

Tagged as: , diabetes, hypoglycemic, KOATP, seizure, SNR