Nov 23, 2019

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

Epilepsia
Pooja Jorwal, Sujit Kumar Sikdar

Abstract

Much evidence suggests that the subiculum plays a significant role in the regulation of epileptic activity. Lactate acts as a neuroprotective agent against many conditions that cause brain damage. During epileptic seizures, lactate formation reaches up to ~6 mmol/L in the brain. We investigated the effect of lactate on subicular pyramidal neurons after induction of epileptiform activity using 4-aminopyridine (4-AP-0Mg2+ ) in an in vitro epilepsy model in rats. The signaling mechanism associated with the suppression of epileptiform discharges by lactate was also investigated. We used patch clamp electrophysiology recordings on rat subicular neurons of acute hippocampal slices. Immunohistochemistry was used for demonstrating the expression of hydroxycarboxylic acid receptor 1 (HCA1) in the subiculum. Our study showed that application of 6 mmol/L lactate after induction of epileptiform activity reduced spike frequency (control 2.5 ± 1.23 Hz vs lactate 1.01 ± 0.91 Hz, P = .049) and hyperpolarized the subicular neurons (control -51.8 ± 1.9 mV vs lactate -57.2 ± 3.56 mV, P = .002) in whole cell patch-clamp experiments. After confirming the expression of HCA1 in subicular neurons, we demonstrated that lactate-mediated effect occurs vi...Continue Reading

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Mentioned in this Paper

Study
Brain Injuries
Patch-Clamp Techniques
Immunohistochemistry
Anticonvulsants
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Regulation of Biological Process
Epilepsy
Neurons
Brain

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