Histamine modulates three types of K+ current in a human intestinal epithelial cell line.
K+ conductance species in a human intestinal epithelial cell line (Intestine 407) were studied in connection with their sensitivities to an intestinal secretagogue, histamine, using the tight-seal whole-cell patch-clamp technique. Applications of positive command pulses rapidly induced outward K+ currents. The conductance became progressively larger with increasing command voltages, exhibiting an outwardly rectifying current voltage relation. Inward K+ currents were also rapidly activated upon applications of hyperpolarizing pulses at potentials negative to the equilibrium potential of K+ (EK), and the conductance inwardly rectified. Application of a Ca2+ ionophore, ionomycin, brought about activation of additional K+ currents. An inhibitor of protein kinase C, polymyxin B, did not affect the ionomycin-induced response. Histamine (10-200 microM) also activated a similar K+ current which was abolished by cytosolic Ca2+ chelation. Under conditions where Ca2+ mobilization was minimized, histamine was found to significantly augment inwardly rectifying K+, but suppress outwardly rectifying K+, currents. Polymyxin B blocked these effects of histamine. An activator of protein kinase C, 1-oleoyl-2-acetylglycerol, mimicked the histamine effects. It is concluded that the intestinal epithelial cell has three distinct types of K+ conductance and that histamine modulates not only Ca(2+)-activated K+ conductance via Ca2+ mobilization, but also inward- and outward-rectifier K+ conductances via activation of protein kinase C.
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
A
A
Itoh
S
S
Ueda
Y
Y
Okada
D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D011493:Protein Kinase C / Q000819:agonists
D004075:Diglycerides; D015759:Ionomycin; D006632:Histamine; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D011112:Polymyxin B; D011188:Potassium; D002118:Calcium