부산대학교 도서관

Molecular characterization of volume-sensitive S[K.sub.Ca] channels in human liver cell lines. Am J Physiol Gastrointest Liver Physiol 282: G116-G122, 2002.--In human liver, [Ca.sup.2+]-dependent changes in membrane [K.sup.+] permeability play a central role in coordinating functional interactions between membrane transport, metabolism, and cell volume. On the basis of the observation that [K.sup.+] conductance is partially sensitive to the bee venom toxin apamin, we aimed to assess whether small-conductance [Ca.sup.2+]-sensitive [K.sup.+] (S[K.sub.Ca]) channels are expressed endogenously and contribute to volume-sensitive [K.sup.+] efflux and cell volume regulation. We isolated a full-length 2,140-bp cDNA (hSK2) highly homologous to rat brain rSK2 cDNA, including the putative apamin-sensitive pore domain, from a human liver cDNA library. Identical cDNAs were isolated from primary human hepatocytes, human HUH-7 hepatoma cells, and human Mz-ChA-1 cholangiocarcinoma cells. Transduction of Chinese hamster ovary cells with a recombinant adenovirus encoding the hSK2-green fluorescent protein fusion construct resulted in expression of functional apamin-sensitive [K.sup.+] channels. In MzChA-1 cells, hypotonic (15% less sodium glutamate) exposure increased K+ current density (1.9 [+ or -] 0.2 to 37.5 [+ or -] 7.1 pA/pF; P < 0.001). Apamin (10-100 nM) inhibited [K.sup.+] current activation and cell volume recovery from swelling. Apamin-sensitive SKca channels are functionally expressed in liver and biliary epithelia and likely contribute to volume-sensitive changes in membrane [K.sup.+] permeability. Accordingly, the hSK2 protein is a potential target for pharmacological modulation of liver transport and metabolism through effects on membrane [K.sup.+] permeability. hepatocyte; cholangiocyte; cell volume; apamin