Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System

Within the potassium ion channel family, calcium activated potassium (K-Ca) channels are unique in their ability to couple intracellular Ca2+ signals to membrane potential variations. K-Ca channels are diversely distributed throughout the central nervous system and play fundamental roles ranging from regulating neuronal excitability to controlling neurotransmitter release. The physiological versatility of K-Ca channels is enhanced by alternative splicing and co-assembly with auxiliary subunits, leading to fundamental differences in distribution, subunit composition and pharmacological profiles. Thus, understanding specific K-Ca channels' mechanisms in neuronal function is challenging. Based on their single channel conductance, K-Ca channels are divided into three subtypes: small (SK, 4-14 pS), intermediate (IK, 32-39 pS) and big potassium (BK, 200-300 pS) channels. This review describes the biophysical characteristics of these K-Ca channels, as well as their physiological roles and pathological implications. In addition, we also discuss the current pharmacological strategies and challenges to target K-Ca channels for the treatment of various neurological and psychiatric disorders.