KCa-Related Neurological Disorders: Phenotypic Spectrum and Therapeutic Indications



Although potassium channelopathies have been linked to a wide range of neurological con-
ditions, the underlying pathogenic mechanism is not always clear, and a systematic summary of clini-
cal manifestation is absent. Several neurological disorders have been associated with alterations of
calcium-activated potassium channels (KCa 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 KCa channels, including big conductance KCa channels
(BK), small conductance KCa channels (SK), and the intermediate conductance KCa channels (IK).
Next, we comprehensively reviewed the loss- or gain-of-function mutations of each KCa channel and
described the corresponding mutation sites in specific diseases to broaden the phenotypic-genotypic
spectrum of KCa-related neurological disorders. Moreover, we reviewed the current pharmaceutical
strategies targeting KCa channels in KCa-related neurological disorders to provide new directions for
drug discovery in anti-seizure medication.
