Control of KCa 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 (KCa) with either micromolar (BKCa channels) or submicromolar (SKCa 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 KCa channels in the CNS. The results may serve as a model for other processes operated by local Ca2+ domains.