Pharmacology of voltage-gated and calcium-activated potassium channels

被引:128
作者
Kaczorowski, GJ [1 ]
Garcia, ML [1 ]
机构
[1] Merck Res Labs, Dept Membrane Biochem & Biophys, Rahway, NJ 07065 USA
关键词
D O I
10.1016/S1367-5931(99)80066-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several important new findings have furthered the development of voltage-gated and calcium-activated potassium channel pharmacology. The molecular constituents of several members of these large ion channel families were identified. Small-molecule modulators of some of these channels were reported, including correolide, the first potent, small-molecule, natural product inhibitor of the Shaker family of voltage-gated potassium channels to be disclosed. The initial crystal structure of a bacterial potassium channel was determined; this work gives a physical basis for understanding the mechanisms of ion selectivity and ion conduction. With the recent molecular characterization of a potassium channel structure and the discovery of new templates for channel modulatory agents, the ability to rationally identify and develop potassium channel agonists and antagonists may become a reality in the near future.
引用
收藏
页码:448 / 458
页数:11
相关论文
共 88 条
  • [1] TOPOLOGY OF THE PORE-REGION OF A K+ CHANNEL REVEALED BY THE NMR-DERIVED STRUCTURES OF SCORPION TOXINS
    AIYAR, J
    WITHKA, JM
    RIZZI, JP
    SINGLETON, DH
    ANDREWS, GC
    LIN, W
    BOYD, J
    HANSON, DC
    SIMON, M
    DETHLEFS, B
    LEE, CL
    HALL, JE
    GUTMAN, GA
    CHANDY, KG
    [J]. NEURON, 1995, 15 (05) : 1169 - 1181
  • [2] Neurobiology of the Caenorhabditis elegans genome
    Bargmann, CI
    [J]. SCIENCE, 1998, 282 (5396) : 2028 - 2033
  • [3] Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo)
    Brandt, T
    Strupp, M
    [J]. AUDIOLOGY AND NEURO-OTOLOGY, 1997, 2 (06) : 373 - 383
  • [4] The SAR of UK-78,282: A novel blocker of human T cell Kv1.3 potassium channels
    Burgess, LE
    Koch, K
    Cooper, K
    Biggers, MS
    Ramchandani, M
    Smitrovich, JH
    Gilbert, EJ
    Bruns, MJ
    Mather, RJ
    Donovan, CB
    Hanson, DC
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (08) : 1047 - 1052
  • [5] Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder?
    Chandy, KG
    Fantino, E
    Wittekindt, O
    Kalman, K
    Tong, LL
    Ho, TH
    Gutman, GA
    Crocq, MA
    Ganguli, R
    Nimgaonkar, V
    Morris-Rosendahl, DJ
    Gargus, JJ
    [J]. MOLECULAR PSYCHIATRY, 1998, 3 (01) : 32 - 37
  • [6] HETEROPOLYMERIC POTASSIUM CHANNELS EXPRESSED IN XENOPUS OOCYTES FROM CLONED SUBUNITS
    CHRISTIE, MJ
    NORTH, RA
    OSBORNE, PB
    DOUGLASS, J
    ADELMAN, JP
    [J]. NEURON, 1990, 4 (03) : 405 - 411
  • [7] Hyperalgesia in mice lacking the Kv1.1 potassium channel gene
    Clark, JD
    Tempel, BL
    [J]. NEUROSCIENCE LETTERS, 1998, 251 (02) : 121 - 124
  • [8] Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels
    Cui, J
    Cox, DH
    Aldrich, RW
    [J]. JOURNAL OF GENERAL PHYSIOLOGY, 1997, 109 (05) : 647 - 673
  • [9] Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle
    DeFarias, FP
    Carvalho, MF
    Lee, SH
    Kaczorowski, GJ
    SuarezKurtz, G
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 314 (1-2) : 123 - 128
  • [10] Role of the S4 segment in a voltage-dependent calcium-sensitive potassium (hSlo) channel
    Díaz, L
    Meera, P
    Amigo, J
    Stefani, E
    Alvarez, O
    Toro, L
    Latorre, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (49) : 32430 - 32436