Chapter Eight - BK Channels in the Central Nervous System
Section snippets
Overview
Large conductance Ca2+-, and voltage-activated K+ channels (also known as BK [for Big Potassium], Maxi-K, or Slo1) are expressed in various tissues. As their name indicates, opening of BK channels leads to a massive efflux of K+ ions that hyperpolarizes cellular membrane potential. This property, combined with their ability to act as a coincidence detector for concomitant elevation in intracellular Ca2+ concentration ([Ca2+]i) and membrane depolarization, puts BK channels in a unique position
Localization
In the mature mammalian CNS, the pore-forming α subunit of BK channels (encoded by the KCNMA1 gene in humans) displays a widespread distribution, as assessed by Northern blot, in situ hybridization, autoradiography, or immunohistochemistry. Prominent levels of expression are observed in the olfactory bulb, cortex, basal ganglia, hippocampus, thalamus, habenulointerpeduncular tract, cerebellum, vestibular nuclei, and spinal cord (Chang et al., 1997, Grunnet and Kaufmann, 2004, Hu et al., 2001,
Neurons
The synergistic effect of depolarization and Ca2+ binding on BK channel opening enables BK channels to act as a coincidence detector (see Chapter “Biophysics of BK Channel Gating” by Pantazis and Olcese), providing a hyperpolarizing drive that contributes to AP repolarization, mediates the fast phase of AHP, and regulates neurotransmitter release and dendritic excitability.
Role of BK Channels in CNS Function and Pathologies
Owing to their multifaceted role in shaping neuronal activity, BK channels help maintain a physiological range of circuit output in the brain and spinal cord. Accordingly, both insufficient and excessive BK channel activity can have detrimental effects on the CNS, as illustrated in Fig. 1. The following section reviews neurological functions and pathologies, in which BK channels have been implicated.
Conclusions
BK channels have myriad (and sometimes opposite) effects on neural activity, as underscored not only by experimental data but also by modeling studies. Their ability to regulate firing output and synaptic transmission depends upon their coexpression and intracellular association with other ion channels, particularly Ca2+ channels, but also HCN and Na+ channels among others. Overall, it is clear that early studies investigating how specific conditions change total levels of BK α transcript or
Acknowledgments
We are grateful for the support of NIH Grants U01 AA-020913 and R21 AA-024198 to C.C., and R21 MH-100612 to A.L.B.
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