Identification of a site that modifies desensitization of P2X2 receptors

被引:25
作者
Zhou, Z [1 ]
Monsma, LR [1 ]
Hume, RI [1 ]
机构
[1] Univ Michigan, Dept Biol, Ann Arbor, MI 48109 USA
关键词
P2X receptors; receptor desensitization; ATP receptors; site directed mutagenesis;
D O I
10.1006/bbrc.1998.9689
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
The time course of desensitization of P2X(2) receptors expressed in Xenopus oocytes and HEK 293 cells was examined. We found that there was virtually no desensitization in response to 5 mu M ATP, but that responses to 50 mu M ATP desensitized with a highly variable time course. The time constant of desensitization varied 250fold among oocytes (from 4 to over 1000 seconds) and 10 fold among HEK cells (from 4 to 40 seconds). Mutation of D349, which lies at the cytoplasmic end of the second transmembrane domain (to either A, N, or R), resulted in a dramatic acceleration of the median rate of desensitization, and eliminated variation in the rate of desensitization. In contrast, mutation of four other charged residues in putative transmembrane domains had no effect on desensitization. These results suggest that P2X(2) receptor desensitization is strongly modulated by the intracellular environment, and that D349 is essential for this modulation. (C) 1998 Academic Press.
引用
收藏
页码:541 / 545
页数:5
相关论文
共 25 条
  • [1] NEW STRUCTURAL MOTIF FOR LIGAND-GATED ION CHANNELS DEFINED BY AN IONOTROPIC ATP RECEPTOR
    BRAKE, AJ
    WAGENBACH, MJ
    JULIUS, D
    [J]. NATURE, 1994, 371 (6497) : 519 - 523
  • [2] Desensitization of the P2X(2) receptor controlled by alternative splicing
    Brandle, U
    Spielmanns, P
    Osteroth, R
    Sim, J
    Surprenant, A
    Buell, G
    Ruppersberg, JP
    Plinkert, PK
    Zenner, HP
    Glowatzki, E
    [J]. FEBS LETTERS, 1997, 404 (2-3) : 294 - 298
  • [3] A P2X PURINOCEPTOR EXPRESSED BY A SUBSET OF SENSORY NEURONS
    CHEN, CC
    AKOPIAN, AN
    SIVILOTTI, L
    COLQUHOUN, D
    BURNSTOCK, G
    WOOD, JN
    [J]. NATURE, 1995, 377 (6548) : 428 - 431
  • [4] Collo G, 1996, J NEUROSCI, V16, P2495
  • [5] DiChiara TJ, 1997, J NEUROSCI, V17, P4942
  • [6] DOWING JEG, 1987, P NATL ACAD SCI USA, V84, P7739
  • [7] Egan TM, 1998, J NEUROSCI, V18, P2350
  • [8] Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ
    Huang, CL
    Feng, SY
    Hilgemann, DW
    [J]. NATURE, 1998, 391 (6669) : 803 - 806
  • [9] PHOSPHORYLATION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR REGULATES ITS RATE OF DESENSITIZATION
    HUGANIR, RL
    DELCOUR, AH
    GREENGARD, P
    HESS, GP
    [J]. NATURE, 1986, 321 (6072) : 774 - 776
  • [10] REGULATION OF RECEPTOR FUNCTION BY PROTEIN-PHOSPHORYLATION
    HUGANIR, RL
    GREENGARD, P
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1987, 8 (12) : 472 - 477