Regulation of gap junctional communication by astrocytic mitochondrial K(ATP) channels following neurotoxin administration in in vitro and in vivo models.

It is known that neuronal ATP-sensitive potassium (K(ATP)) channels and astrocytic gap junctions (GJs) are involved in the mechanism underlying neurodisorders. The K(ATP) channels exist also in glial cells, and the objective of this study was to determine whether the astrocytic K(ATP) channels exert their effect on neurotoxin-induced neurodysfunction through regulating the astrocytic GJ function. The results showed that diazoxide, a selective mitochondrial K(ATP) (mitoK(ATP)) channel opener, enhanced the GJ coupling, but 5-hydroxydecanoate, a selective mitoK(ATP) channel blocker that significantly inhibits GJ coupling in vitro did not. Activation of astrocytic mitoK(ATP) channels alleviated kainic acid-induced dysfunction of GJ intercellular communication. Finally, activation of mitoK(ATP) channels improved the astrocytic GJ coupling in the hippocampus after seizures due to the colabeling of GJ subunit connexin 43 and connexin 45 with glial marker and was increased substantially by the administration of diazoxide. Western blot demonstrated that the mitoK(ATP) channels regulated the expression of connexin 43 (P2; active form) and connexin 45 in the epileptic hippocampus. These findings demonstrate that activation of astrocytic mitoK(ATP) channels improves the GJ function in astrocytes, indicating that the effect of the astrocytic mitoK(ATP) channels on neurotoxin-induced neurodysfunction might be, in part, through the regulation of the GJ-coupled spatial buffering in the hippocampus.