Potassium channels in behavioral brain disorders. Molecular mechanisms and therapeutic potential: A narrative review

Abstract

Potassium channels (K⁺-channels) selectively control the passive flow of potassium ions across biological membranes and thereby also regulate membrane excitability. Genetic variants affecting many of the human K⁺-channels are well known causes of Mendelian disorders within cardiology, neurology, and endocrinology. K⁺-channels are also primary targets of many natural toxins from poisonous organisms and drugs used within cardiology and metabolism. As genetic tools are improving and larger clinical samples are being investigated, the spectrum of clinical phenotypes implicated in K⁺-channels dysfunction is rapidly expanding, notably within immunology, neurosciences, and metabolism. K⁺-channels that previously were considered to be expressed in only a few organs and to have discrete physiological functions, have recently been found in multiple tissues and with new, unexpected functions. The pleiotropic functions and patterns of expression of K⁺-channels may provide additional therapeutic opportunities, along with new emerging challenges from off-target effects. Here we review the functions and therapeutic potential of K⁺-channels, with an emphasis on the nervous system, roles in neuropsychiatric disorders and their involvement in other organ systems and diseases.

Keywords: Ataxia; Diabetes; Epilepsy; Insulin; Ligands; Long QT syndrome; Neuropsychiatric disorders; Obsessive compulsive disorder (OCD); Pharmacology; Potassium channel.