The pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines

被引:98
作者
Shah, M [1 ]
Haylett, DG [1 ]
机构
[1] UCL, Dept Pharmacol, London WC1E 6BT, England
基金
英国惠康基金;
关键词
SK1; apamin; tubocurarine; dequalinium; UCL1848; HEK293; cells; COS-7; afterhyperpolarization;
D O I
10.1038/sj.bjp.0703111
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The pharmacology of hSK1, a small conductance calcium-activated potassium channel, was studied in mammalian cell lines (HEK293 and COS-7). In these cell types, hSK1 forms an apamin-sensitive channel with an IC50 for apamin of 8 nM in HEK293 cells and 12 nM in COS-7 cells. The currents in HEK293 cells were also sensitive to tubocurarine (IC50 = 23 mu M), dequalinium (IC50 = 0.4 mu M), and the novel dequalinium analogue, UCL1848 (IC50 = 1 nM). These results are very different from the pharmacology of hSK1 channels expressed in Xenopus oocytes and suggest the properties of the channel may depend on the expression system. Our findings also raise questions about the role of SK1 channels in generating the apamin-insensitive slow afterhyperpolarization observed in central neurones.
引用
收藏
页码:627 / 630
页数:4
相关论文
共 16 条
  • [1] Benton DCH, 1999, BRIT J PHARMACOL, V128
  • [2] DEQUALINIUM - A POTENT INHIBITOR OF APAMIN-SENSITIVE K(+) CHANNELS IN HEPATOCYTES AND OF NICOTINIC RESPONSES IN SKELETAL-MUSCLE
    CASTLE, NA
    HAYLETT, DG
    MORGAN, JM
    JENKINSON, DH
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1993, 236 (02) : 201 - 207
  • [3] DEQUALINIUM, A SELECTIVE BLOCKER OF THE SLOW AFTERHYPERPOLARIZATION IN RAT SYMPATHETIC NEURONS IN CULTURE
    DUNN, PM
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 252 (02) : 189 - 194
  • [4] Discrimination between subtypes of apamin-sensitive Ca2+-activated K+ channels by gallamine and a novel bis-quaternary quinolinium cyclophane, UCL 1530
    Dunn, PM
    Benton, DCH
    Rosa, JC
    Ganellin, CR
    Jenkinson, DH
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (01) : 35 - 42
  • [5] HOSSEINI R, 1999, J PHYSL, V518, pP122
  • [6] Determinants of apamin and d-tubocurarine block in SK potassium channels
    Ishii, TM
    Maylie, J
    Adelman, JP
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (37) : 23195 - 23200
  • [7] JURMAN ME, 1994, BIOTECHNIQUES, V17, P876
  • [8] Bicuculline block of small-conductance calcium-activated potassium channels
    Khawaled, R
    Bruening-Wright, A
    Adelman, JP
    Maylie, J
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1999, 438 (03): : 314 - 321
  • [9] Small-conductance, calcium-activated potassium channels from mammalian brain
    Kohler, M
    Hirschberg, B
    Bond, CT
    Kinzie, JM
    Marrion, NV
    Maylie, J
    Adelman, JP
    [J]. SCIENCE, 1996, 273 (5282) : 1709 - 1714
  • [10] The ion channel properties of a rat recombinant neuronal nicotinic receptor are dependent on the host cell type
    Lewis, TM
    Harkness, PC
    Sivilotti, LG
    Colquhoun, D
    Millar, NS
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1997, 505 (02): : 299 - 306