KCa-Related Neurological Disorders: Phenotypic Spectrum and Therapeutic Indications

Abstract

Although potassium channelopathies have been linked to a wide range of neurological conditions, the underlying pathogenic mechanism is not always clear, and a systematic summary of clinical manifestation is absent. Several neurological disorders have been associated with alterations of calcium-activated potassium channels (K_Ca channels), such as loss- or gain-of-function mutations, post-transcriptional modification, etc. Here, we outlined the current understanding of the molecular and cellular properties of three subtypes of K_Ca channels, including big conductance K_Ca channels (BK), small conductance K_Ca channels (SK), and the intermediate conductance K_Ca channels (IK). Next, we comprehensively reviewed the loss- or gain-of-function mutations of each K_Ca channel and described the corresponding mutation sites in specific diseases to broaden the phenotypic-genotypic spectrum of K_Ca-related neurological disorders. Moreover, we reviewed the current pharmaceutical strategies targeting K_Ca channels in K_Ca-related neurological disorders to provide new directions for drug discovery in anti-seizure medication.

Keywords: Potassium channels; action potential; channelopathies; epilepsy; modulators; pharmacology.