Abstract
Within the potassium ion channel family, calcium activated potassium (KCa) channels are unique in their ability to couple intracellular Ca2+ signals to membrane potential variations. KCa 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 KCa 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 KCa channels’ mechanisms in neuronal function is challenging. Based on their single channel conductance, KCa 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 KCa channels, as well as their physiological roles and pathological implications. In addition, we also discuss the current pharmacological strategies and challenges to target KCa channels for the treatment of various neurological and psychiatric disorders.
Highlights
Ca2+-activated potassium channels (KCa channels) constitute a heterogeneous family of ion channels with variable biophysical and pharmacological properties
We summarize the most recent knowledge about KCa channels, focusing on their potential as therapeutic targets in the nervous system and analyzing the factors that could contribute to the difficulties to develop novel KCa channel modulators
involving KCa3.1 (IK) channels have been related to microglia activation by modulating Ca2+ signaling, oxidative burst, proinflammatory cytokines production and microglia-mediated neuronal cell death (Kaushal et al, 2007). According to these proposed physiological roles, a recent study demonstrated that genetic ablation or in vivo pharmacological blockade of IK channels in the middle cerebral artery occlusion (MCAO) mouse model reduced the infarct area as well as improved neurological deficit by reducing microglia-associated neuronal death (Chen Y.J. et al, 2016)
Summary
Ca2+-activated potassium channels (KCa channels) constitute a heterogeneous family of ion channels with variable biophysical and pharmacological properties. BK channels are localized throughout the dendrites, axon, soma and synaptic terminals of neurons in different brain regions, including cortex and hippocampus (Knaus et al, 1996; Grunnet and Kaufmann, 2004; Wang et al, 2014), where they play key roles in action potential duration, firing frequency and neurotransmitter release (for a recent review, see Contet et al, 2016).
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