SELECTIVE POTENTIATION OF GABA-MEDIATED CL- CURRENT BY LANTHANUM ION IN SUBTYPES OF CLONED GABA-A RECEPTORS

被引:42
作者
IM, MS [1 ]
HAMILTON, BJ [1 ]
CARTER, DB [1 ]
IM, WB [1 ]
机构
[1] UPJOHN CO,CNR DIS RES,KALAMAZOO,MI 49001
关键词
CLONED GABA-A RECEPTOR; SUBUNIT COMPOSITION; LANTHANUM; SELECTIVE POTENTIATION; GABA-INDUCED CL- CURRENT;
D O I
10.1016/0304-3940(92)90741-O
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The effect of lanthanum ion (La3+) on gamma-aminobutyric acid (GABA)-mediated Cl- currents was examined in the alpha1beta2 or alpha1beta2gamma2 subtype of GABA(A) receptors expressed in a human kidney cell line (A293), using a whole-cell configuration of patch-clamp techniques. La3+ dose-dependently stimulated the Cl- currents in the alpha1beta2gamma2 subtype with an EC50 of 21.3 +/- 3.5 muM with a maximal potentiation of 240 +/- 16% as normalized to the GABA response at 5 muM. In the alpha1beta2 subtype, however, the ion marginally potentiated GABA response, a maximal stimulation being less than 70% with an EC50 for La3+ near 200 muM. The stimulation of GABA response by La3+ in the alpha1beta2gamma2 Subtype was due to a decrease in the half maximal concentration for GABA and was more pronounced at the negative membrane potentials. This selectivity of La3+ toward the subtypes of GABA(A) receptors contrasts to that of Zn2+ which inhibits the currents in the alpha1beta2, but not in the alpha1beta2gamma2 subtype (Neuron, 5: (1990) 781 788). It appears that these polyvalent cations are useful in understanding the molecular basis for the functional diversity and in characterizing the molecular organization of native GABA(A) receptors.
引用
收藏
页码:165 / 168
页数:4
相关论文
共 25 条
[1]   MULTIPLE MECHANISMS OF ANTAGONISM OF GAMMA-AMINOBUTYRIC-ACID (GABA) RESPONSES [J].
AKAIKE, N ;
YAKUSHIJI, T ;
TOKUTOMI, N ;
CARPENTER, DO .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 1987, 7 (01) :97-103
[2]   MOLECULAR-BIOLOGY OF THE GABA-A RECEPTOR - THE RECEPTOR CHANNEL SUPERFAMILY [J].
BARNARD, EA ;
DARLISON, MG ;
SEEBURG, P .
TRENDS IN NEUROSCIENCES, 1987, 10 (12) :502-509
[3]   FUNCTIONAL AND MOLECULAR DISTINCTION BETWEEN RECOMBINANT RAT GABA-A RECEPTOR SUBTYPES BY ZN-2+ [J].
DRAGUHN, A ;
VERDORN, TA ;
EWERT, M ;
SEEBURG, PH ;
SAKMANN, B .
NEURON, 1990, 5 (06) :781-788
[4]   CHARACTERISTICS OF A HUMAN CELL LINE TRANSFORMED BY DNA FROM HUMAN ADENOVIRUS TYPE-5 [J].
GRAHAM, FL ;
SMILEY, J ;
RUSSELL, WC ;
NAIRN, R .
JOURNAL OF GENERAL VIROLOGY, 1977, 36 (JUL) :59-72
[5]   A NOVEL-ALPHA-SUBUNIT IN RAT-BRAIN GABAA RECEPTORS [J].
KHRESTCHATISKY, M ;
MACLENNAN, AJ ;
CHIANG, MY ;
XU, WT ;
JACKSON, MB ;
BRECHA, N ;
STERNINI, C ;
OLSEN, RW ;
TOBIN, AJ .
NEURON, 1989, 3 (06) :745-753
[6]  
LEGENDRE P, 1991, MOL PHARMACOL, V39, P267
[7]   STRUCTURAL AND FUNCTIONAL BASIS FOR GABAA RECEPTOR HETEROGENEITY [J].
LEVITAN, ES ;
SCHOFIELD, PR ;
BURT, DR ;
RHEE, LM ;
WISDEN, W ;
KOHLER, M ;
FUJITA, N ;
RODRIGUEZ, HF ;
STEPHENSON, A ;
DARLISON, MG ;
BARNARD, EA ;
SEEBURG, PH .
NATURE, 1988, 335 (6185) :76-79
[8]   HIGH-LEVEL EXPRESSION OF NONFUSED FOREIGN GENES WITH AUTOGRAPHA-CALIFORNICA NUCLEAR POLYHEDROSIS-VIRUS EXPRESSION VECTORS [J].
LUCKOW, VA ;
SUMMERS, MD .
VIROLOGY, 1989, 170 (01) :31-39
[9]   THE ACTION OF ZINC ON SYNAPTIC TRANSMISSION AND NEURONAL EXCITABILITY IN CULTURES OF MOUSE HIPPOCAMPUS [J].
MAYER, ML ;
VYKLICKY, L .
JOURNAL OF PHYSIOLOGY-LONDON, 1989, 415 :351-365
[10]   MOLECULAR-BIOLOGY OF GABA-A RECEPTORS [J].
OLSEN, RW ;
TOBIN, AJ .
FASEB JOURNAL, 1990, 4 (05) :1469-1480