Altered GABA(A) receptor expression during epileptogenesis

Abstract

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA(A) receptors are heteropentamers formed by assembly of multiple subunits that generate a wide array of receptors with particular distribution and pharmacological profiles. Malfunction of these receptors has been associated with the pathophysiology of epilepsy and contribute to an imbalance of excitatory and inhibitory neurotransmission. The process of epilepsy development (epileptogenesis) is associated with changes in the expression and function of a large number of gene products. One of the major challenges is to effectively determine which changes directly contribute to epilepsy development versus those that are compensatory or not involved in the pathology. Substantial evidence suggests that changes in the expression and function of GABA(A) receptors are involved in the pathogenesis of epilepsy. Identification of the mechanisms involved in GABA(A) receptor malfunction during epileptogenesis and the ability to reverse this malfunction are crucial steps towards definitively answering this question and developing specific and effective therapies.