SINGLE AMINO-ACID SUBSTITUTION AFFECTS DESENSITIZATION OF THE 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTOR EXPRESSED IN XENOPUS-OOCYTES

被引:120
作者
YAKEL, JL
LAGRUTTA, A
ADELMAN, JP
NORTH, RA
机构
[1] Vollum Institute, Oregon Health Sciences University, Portland
关键词
SITE-DIRECTED MUTAGENESIS; LIGAND-GATED ION CHANNEL;
D O I
10.1073/pnas.90.11.5030
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
5-Hydroxytryptamine type 3 receptors were expressed in Xenopus oocytes from a cloned cDNA. The peak inward current evoked by 5-hydroxytryptamine (30 muM) was linearly related to the holding potential (-100 to +20 mV) and reversed near 0 mV. The inward current (at -60 mV) declined during the continued presence of 5-hydroxytryptamine with a half-time of about 2 s; this desensitization was 20 times slower in calcium-free solution. Desensitization was markedly different in channels in which Leu286 was changed by site-directed mutagenesis; this residue is thought to lie near the middle of the M2 segment. Desensitization was faster with Phe, Tyr, or Ala in this position and slower with Thr. Phe and Thr substitutions in the equivalent position of the nicotinic acetylcholine receptor have similar effects on desensitization, suggesting that the underlying conformational change might be common to ligand-gated channels.
引用
收藏
页码:5030 / 5033
页数:4
相关论文
共 32 条
[21]   MUTATIONS IN THE CHANNEL DOMAIN ALTER DESENSITIZATION OF A NEURONAL NICOTINIC RECEPTOR [J].
REVAH, F ;
BERTRAND, D ;
GALZI, JL ;
DEVILLERSTHIERY, A ;
MULLE, C ;
HUSSY, N ;
BERTRAND, S ;
BALLIVET, M ;
CHANGEUX, JP .
NATURE, 1991, 353 (6347) :846-849
[22]   PROPERTIES OF 5-HYDROXYTRYPTAMINE3 RECEPTOR-GATED CURRENTS IN ADULT-RAT DORSAL-ROOT GANGLION NEURONS [J].
ROBERTSON, B ;
BEVAN, S .
BRITISH JOURNAL OF PHARMACOLOGY, 1991, 102 (01) :272-276
[23]   BRAIN ALPHA-BUNGAROTOXIN BINDING-PROTEIN CDNAS AND MABS REVEAL SUBTYPES OF THIS BRANCH OF THE LIGAND-GATED ION CHANNEL GENE SUPERFAMILY [J].
SCHOEPFER, R ;
CONROY, WG ;
WHITING, P ;
GORE, M ;
LINDSTROM, J .
NEURON, 1990, 5 (01) :35-48
[24]   DIFFERENTIATION OF NG108-15 CELLS ALTERS CHANNEL CONDUCTANCE AND DESENSITIZATION KINETICS OF THE 5-HT3 RECEPTOR [J].
SHAO, XM ;
YAKEL, JL ;
JACKSON, MB .
JOURNAL OF NEUROPHYSIOLOGY, 1991, 65 (03) :630-638
[25]   GLUTAMATE RECEPTOR DESENSITIZATION AND ITS ROLE IN SYNAPTIC TRANSMISSION [J].
TRUSSELL, LO ;
FISCHBACH, GD .
NEURON, 1989, 3 (02) :209-218
[26]   THE STRUCTURE OF ION CHANNELS IN MEMBRANES OF EXCITABLE CELLS [J].
UNWIN, N .
NEURON, 1989, 3 (06) :665-676
[27]   MODULATION OF EXCITATORY SYNAPTIC TRANSMISSION BY DRUGS THAT REDUCE DESENSITIZATION AT AMPA KAINATE RECEPTORS [J].
VYKLICKY, L ;
PATNEAU, DK ;
MAYER, ML .
NEURON, 1991, 7 (06) :971-984
[28]   5-HT3 RECEPTORS MEDIATE RAPID RESPONSES IN CULTURED HIPPOCAMPUS AND A CLONAL CELL-LINE [J].
YAKEL, JL ;
JACKSON, MB .
NEURON, 1988, 1 (07) :615-621
[29]   ACTIVATION AND DESENSITIZATION OF THE 5-HT3 RECEPTOR IN A RAT GLIOMA X MOUSE NEUROBLASTOMA HYBRID CELL [J].
YAKEL, JL ;
SHAO, XM ;
JACKSON, MB .
JOURNAL OF PHYSIOLOGY-LONDON, 1991, 436 :293-308
[30]   THE SELECTIVITY OF THE CHANNEL COUPLED TO THE 5-HT3 RECEPTOR [J].
YAKEL, JL ;
SHAO, XM ;
JACKSON, MB .
BRAIN RESEARCH, 1990, 533 (01) :46-52