High-conductance calcium-activated potassium channels: validated targets for smooth muscle relaxants?

被引:14
|
作者
Garcia, Maria L. [1 ]
Shen, Dong-Ming [1 ]
Kaczorowski, Gregory J. [1 ]
机构
[1] Merck Res Labs, Dept Ion Channels, Rahway, NJ 07065 USA
关键词
erectile dysfunction; Maxi-K channel openers; smooth muscle relaxation; urinary incontinence; vasorelaxation;
D O I
10.1517/13543776.17.7.831
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
High-conductance, calcium-activated potassium (Maxi-K) channels represent a group of proteins with diverse physiologic functions. Although the role of Maxi-K channels in the CNS is complex and still an area of active academic research, there appears to be better agreement concerning the contribution of these channels to the regulation of smooth muscle tone and, thus the expectations remain high for Maxi-K channel openers having use in the treatment of hypertension, overactive bladder, asthma or erectile dysfunction. Despite this consensus view, at the present time, there is only one compound that targets Maxi-K channels in clinical development for overactive bladder conditions. In the present review, the latest developments in the identification of potent and selective Maxi-K channel openers and their utility in the treatment of smooth muscle disorders will be discussed.
引用
收藏
页码:831 / 842
页数:12
相关论文
共 50 条
  • [1] Selective, Direct Activation of High-Conductance, Calcium-Activated Potassium Channels Causes Smooth Muscle Relaxation
    Ponte, Cristiano G.
    McManus, Owen B.
    Schmalhofer, William A.
    Shen, Dong-Ming
    Dai, Ge
    Stevenson, Andra
    Sur, Sylvie
    Shah, Tarak
    Kiss, Laszlo
    Shu, Min
    Doherty, James B.
    Nargund, Ravi
    Kaczorowski, Gregory J.
    Suarez-Kurtz, Guilherme
    Garcia, Maria L.
    MOLECULAR PHARMACOLOGY, 2012, 81 (04) : 567 - 577
  • [2] PHARMACOLOGY AND STRUCTURE OF HIGH-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
    KNAUS, HG
    EBERHART, A
    GLOSSMANN, H
    MUNUJOS, P
    KACZOROWSKI, GJ
    GARCIA, ML
    CELLULAR SIGNALLING, 1994, 6 (08) : 861 - &
  • [3] TREMORGENIC INDOLE ALKALOIDS POTENTLY INHIBIT SMOOTH-MUSCLE HIGH-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
    KNAUS, HG
    MCMANUS, OB
    LEE, SH
    SCHMALHOFER, WA
    GARCIACALVO, M
    HELMS, LMH
    SANCHEZ, M
    GIANGIACOMO, K
    REUBEN, JP
    SMITH, AB
    KACZOROWSKI, GJ
    GARCIA, ML
    BIOCHEMISTRY, 1994, 33 (19) : 5819 - 5828
  • [4] High-conductance calcium-activated potassium channels; Structure, pharmacology, and function
    Kaczorowski, GJ
    Knaus, HG
    Leonard, RJ
    McManus, OB
    Garcia, ML
    JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1996, 28 (03) : 255 - 267
  • [5] Distribution of High-Conductance Calcium-Activated Potassium Channels in Rat Vestibular Epithelia
    Schweizer, Felix E.
    Savin, David
    Luu, Cindy
    Sultemeier, David R.
    Hoffman, Larry F.
    JOURNAL OF COMPARATIVE NEUROLOGY, 2009, 517 (02) : 134 - 145
  • [6] PURIFICATION AND RECONSTITUTION OF THE HIGH-CONDUCTANCE, CALCIUM-ACTIVATED POTASSIUM CHANNEL FROM TRACHEAL SMOOTH-MUSCLE
    GARCIACALVO, M
    KNAUS, HG
    MCMANUS, OB
    GIANGIACOMO, KM
    KACZOROWSKI, GJ
    GARCIA, ML
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1994, 269 (01) : 676 - 682
  • [7] SUBUNIT COMPOSITION OF THE HIGH-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL FROM SMOOTH-MUSCLE, A REPRESENTATIVE OF THE MSLO AND SLOWPOKE FAMILY OF POTASSIUM CHANNELS
    KNAUS, HG
    GARCIACALVO, M
    KACZOROWSKI, GJ
    GARCIA, ML
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1994, 269 (06) : 3921 - 3924
  • [8] Inhibition of high-conductance, calcium-activated potassium channels of rabbit colon epithelium by magnesium
    Wachter, C
    Turnheim, K
    JOURNAL OF MEMBRANE BIOLOGY, 1996, 150 (03): : 275 - 282
  • [9] High-conductance calcium-activated potassium channels in rat brain: Pharmacology, distribution, and subunit composition
    Wanner, SG
    Koch, RO
    Koschak, A
    Trieb, M
    Garcia, ML
    Kaczorowski, GJ
    Knaus, HG
    BIOCHEMISTRY, 1999, 38 (17) : 5392 - 5400
  • [10] FUNCTIONAL-ROLE OF THE BETA-SUBUNIT OF HIGH-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
    MCMANUS, OB
    HELMS, LMH
    PALLANCK, L
    GANETZKY, B
    SWANSON, R
    LEONARD, RJ
    NEURON, 1995, 14 (03) : 645 - 650