SINGLE-CHANNEL ACTIVITY IN CULTURED CORTICAL-NEURONS OF THE RAT IN THE PRESENCE OF A TOXIC DOSE OF GLUTAMATE

被引:9
作者
BACKUS, KH [1 ]
TRUBE, G [1 ]
机构
[1] F HOFFMANN LA ROCHE & CO LTD, PRECLIN RES, DIV PHARMA, CH-4002 BASEL, SWITZERLAND
关键词
GLUTAMATE RECEPTOR; CALCIUM-ACTIVATED POTASSIUM CHANNEL; NEUROTOXICITY; PATCH-CLAMP;
D O I
10.1111/j.1460-9568.1993.tb00483.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Rat cortical neurons grown in cell culture were exposed to 500 muM glutamate for 5 min during continuous current recording from cell-attached patches. The Ca2+-dependence and ion selectivity of the membrane channels activated during and after glutamate application were studied in inside-out patches. Glutamate blocked spontaneous action potential firing. In 77% of the experiments glutamate activated several types of ion channels indirectly, i.e. via a change of cytoplasmic factors. Channel activity did not disappear after removing glutamate from the bath. A K+ channel requiring intracellular calcium ([Ca2+]i) was activated in 44% of the experiments (conductance for inward currents in cell-attached patches 118 +/- 6 pS; 'BK channel'). Another Ca2+-dependent channel permeable for Cl- (conductance for outward currents in cell-attached patches 72 +/- 17 pS), acetate and methanesulphonate appeared in 26% of the patches. Other K+ channels of smaller conductance were infrequently observed. During and after glutamate application the activity of the BK channel showed an initial increase followed by a transient decay and a second rise to a plateau, probably reflecting a similar time course of changes in [Ca2+]i. Both phases of increasing channel activity required the presence of extracellular Ca2+ suggesting that [Ca2+]i was mainly increased by Ca2+ influx. The N-methyl-D-aspartate (NMDA) antagonists dizocilpine (MK-801, 10 muM) and DL-2-amino-5-phosphonovaleric acid (AP5; 100 muM), added within 5 min after glutamate application, stopped BK channel activity and restored the spontaneous action potential firing. We conclude that the influx of Ca2+ through NMDA receptor channels causes a strong activation of Ca2+-dependent K+ channels, which is likely to result in pronounced loss of intracellular K+. NMDA receptor channels seem to remain active for a long time (> 10 min) after the end of glutamate application.
引用
收藏
页码:174 / 185
页数:12
相关论文
共 41 条
[1]  
BACKUS KH, 1990, PFLUGERS ARCH S, V342, pR1
[2]   PROPERTIES OF SINGLE CALCIUM-ACTIVATED POTASSIUM CHANNELS IN CULTURED RAT MUSCLE [J].
BARRETT, JN ;
MAGLEBY, KL ;
PALLOTTA, BS .
JOURNAL OF PHYSIOLOGY-LONDON, 1982, 331 (OCT) :211-230
[3]  
CHEUNG JY, 1986, NEW ENGL J MED, V314, P1670
[4]   GLUTAMATE NEUROTOXICITY IN CORTICAL CELL-CULTURE IS CALCIUM DEPENDENT [J].
CHOI, DW .
NEUROSCIENCE LETTERS, 1985, 58 (03) :293-297
[5]  
CHOI DW, 1988, J NEUROSCI, V8, P185
[7]  
CHOI DW, 1987, J NEUROSCI, V7, P369
[8]  
CHOI DW, 1987, J NEUROSCI, V7, P357
[9]  
CONNOR JA, 1987, J NEUROSCI, V7, P1384
[10]  
COYLE JT, 1981, NEUROSCI RES PROG B, V19, pU335