Control of K_Ca Channels by Calcium Nano/Microdomains

Transient elevations in cytoplasmic Ca²⁺ trigger a multitude of Ca²⁺-dependent processes in CNS neurons and many other cell types. The specificity, speed, and reliability of these processes is achieved and ensured by tightly restricting Ca²⁺ signals to very local spatiotemporal domains, "Ca²⁺ nano- and microdomains," that are centered around Ca²⁺-permeable channels. This arrangement requires that the Ca²⁺-dependent effectors reside within these spatial boundaries where the properties of the Ca²⁺ domain and the Ca²⁺ sensor of the effector determine the channel-effector activity. We use Ca²⁺-activated K⁺ channels (K_Ca) with either micromolar (BK_Ca channels) or submicromolar (SK_Ca channels) affinity for Ca²⁺ ions to provide distance constraints for Ca²⁺-effector coupling in local Ca²⁺ domains and review their significance for the cell physiology of K_Ca channels in the CNS. The results may serve as a model for other processes operated by local Ca²⁺ domains.