Role of Ion Channelopathy in Neurological Diseases; Role of Gabaergic System Connectivity and Dysfunction in Neurological Disorders

Abstract

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is produced by GABAergic neurons and is essential in human neurodevelopmental stage. It has a variety of functions in the CNS and exerts its functions by binding to several GABA receptors including ionotropic and ligand-gated chloride channels. The CNS neurotransmitters endorphin, dopamine, serotonin or 5-hydroxytryptamine (5-HT), norepinephrine (NE), and acetylcholine (ACh) are all regulated by GABA. Additionally, GABA has a role in the pathogenesis of some CNS-related diseases. This study discusses the function of GABA in human neurodevelopmental stages and its interactions with other CNS neurotransmitters. The significance of Cl- homeostasis in GABA receptor activities, which regulate Cl--mediated neurotransmission in the CNS, is also stressed. Furthermore, the relationship between intracellular Cl- changes and CNS diseases such as Down syndrome (DS), epilepsy, schizophrenia, and autism spectrum disorders (ASD) is discussed. The study also highlights the potential application of bumetanide to regulate intracellular Cl- levels and treat CNS disease symptoms. The article comes to the conclusion that understanding the function of GABA and chloride homeostasis in clinical CNS diseases is beneficial in developing innovative treatment options, and the potential of bumetanide offers a new direction for research and clinical intervention.