Lactate reduces epileptiform activity through HCA1 and GIRK channel activation in rat subicular neurons in an in vitro model

摘要: OBJECTIVE Much evidence suggests that the subiculum plays a significant role in regulation of epileptic activity. Lactate acts as neuroprotective agent against many conditions cause brain damage. During seizures, lactate formation reaches up to ~6 mmol/L brain. We investigated effect on subicular pyramidal neurons after induction epileptiform activity using 4-aminopyridine (4-AP-0Mg2+ ) an vitro epilepsy model rats. The signaling mechanism associated with suppression discharges by was also investigated. METHODS used patch clamp electrophysiology recordings rat acute hippocampal slices. Immunohistochemistry for demonstrating expression hydroxycarboxylic acid receptor 1 (HCA1) subiculum. RESULTS Our study showed application 6 mmol/L reduced spike frequency (control 2.5 ± 1.23 Hz vs 1.01 ± 0.91 Hz, P = .049) and hyperpolarized -51.8 ± 1.9 mV -57.2 ± 3.56 mV, P = .002) whole cell patch-clamp experiments. After confirming HCA1 neurons, we demonstrated lactate-mediated occurs via its specific agonist. All values are mean ±SD. Electrophysiological revealed involvement Gβγ intracellular cAMP lactate-induced effect. Furthermore, current-clamp voltage-clamp experiments G protein-coupled inwardly rectifying potassium (GIRK) channel blocker tertiapin-Q, negated inhibitory effect, which confirmed results outward GIRK current. SIGNIFICANCE finding points toward potential anticonvulsant showing neurons. gives different insight suggesting importance endogenous metabolite factors, can aid improving present therapeutic approach treating epilepsy.