Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Kv channel-interacting proteins (KChIPs) belong to the neuronal calcium sensor (NCS) family of Ca²⁺-binding EF-hand proteins. KChIPs constitute a group of specific auxiliary β-subunits for Kv4 channels, the molecular substrate of transient potassium currents in both neuronal and non-neuronal tissues. Moreover, KChIPs can interact with presenilins to control ER calcium signaling and apoptosis, and with DNA to control gene transcription. Ca²⁺ binding via their EF-hands, with the consequence of conformationl changes, is well documented for KChIPs. Moreover, the Ca²⁺ dependence of the presenilin/KChIP complex may be related to Alzheimer's disease and the Ca²⁺ dependence of the DNA/KChIP complex to pain sensing. However, only in few cases could the Ca²⁺ binding to KChIPs be directly linked to the control of excitability in nerve and muscle cells known to express Kv4/KChIP channel complexes. This review summarizes current knowledge about the Ca²⁺ binding properties of KChIPs and the Ca²⁺ dependencies of macromolecular complexes containing KChIPs, including those with presenilins, DNA and especially Kv4 channels. The respective physiological or pathophysiolgical roles of Ca²⁺ binding to KChIPs are discussed.