抄録
Voltage-dependent K+ channels are classified into two categories, 'delayed rectifier-type' and 'rapidly-inactivating A-type'. A-type K+ channel plays an important role in the control of action potential threshold, frequency, and duration in smooth muscles, which possess relatively high membrane excitability such as colon, portal vein, ureter and vas deferens. We showed that Kv4.3L, a longer isoform of Kv4.3, predominantly contributes to A-type K+ channel α subunit in smooth muscles. Additionally, regulatory β subunits of Kv4 channels, which promote the trafficking of Kv4 channels to plasma membrane and also modulate their kinetics, have been identified as neuronal Ca2+-binding proteins (NCBPs) with high similarity to calmodulin (CaM). We also identified that KChIP1, KChIP3, and NCS-1 are the major components of NCBPs in vascular and visceral smooth muscles. CaM-dependent kinase II (CaMKII) slows the inactivation of A-type K+ currents in mouse colonic smooth muscle cells. Similarly, autothiophosphorylated CaMKII slowed the Kv4.3 currents and affected the inactivation kinetics of Kv4.3 channels. In addition, the mutation of Ca2+-binding EF motif in KChIP did not affect the kinetics of Kv4 channels. Using site-directed mutagenesis, we suggested that CaMKII regulates A-type K+ current kinetics by direct phosphorylation of Kv4.3 at Ser550 on the C-terminus but not at Thr53 on N-terminus. [J Physiol Sci. 2008;58 Suppl:S45]
