K(Ca)-Related Neurological Disorders: Phenotypic Spectrum and Therapeutic Indications

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.