Changes in intracellular Ca2+ induced by GABAA receptor activation and reduction in Cl- gradient in neonatal rat neocortex

被引:73
作者
Fukuda, A [1 ]
Muramatsu, K [1 ]
Okabe, A [1 ]
Shimano, Y [1 ]
Hida, H [1 ]
Fujimoto, I [1 ]
Nishino, H [1 ]
机构
[1] Nagoya City Univ, Sch Med, Dept Physiol, Mizuho Ku, Nagoya, Aichi 467, Japan
关键词
D O I
10.1152/jn.1998.79.1.439
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Changes in intracellular Ca2+ induced by GABA, receptor activation and reduction in Cl- gradient in neonatal rat neocortex. J. Neurophysiol. 79: 439-446, 1998. We have studied the effects of gamma-aminobutyric acid (GABA) and of reducing the Cl- gradient on the [Ca2+](i) in pyramidal neurons of rat somatosensory cortex. The Cl-gradient was reduced either with furosemide or by oxygen glucose deprivation. Immature slices taken at postnatal day (P) 7-14 were labeled with fura-2, and [Ca2+](i) was monitored in identified pyramidal cells in layer II/III as the ratio of fluorescence intensities (R-F340/F380) The magnitude of the [Ca2+](i) increases induced by oxygen-glucose deprivation was significantly reduced (by 44%) by bicuculline (10 mu M), a GABA(A) receptor antagonist. Under normal conditions, GABA generally did not raise [Ca2+](i), although in some neurons a small and transient [Ca2+]i increase was observed. These transient [Ca2+](i) increases were blocked by Ni2+ (1 mM), a blocker of voltage-dependent Ca2+ channels (VDCCs). Continuous perfusion with GABA did not cause a sustained elevation of [Ca2+](i) but bicuculline caused [Ca2+](i) oscillations. After inhibition of Cl-extrusion with furosemide (1.5 mM), GABA induced a large [Ca2+](i) increase consisting of an initial peak followed by a sustained phase. Both the initial and the sustained phases were eliminated by bicuculline(10 mu M). The initial but not the sustained phase was abolished by Ni2+. In the presence of Ni2+, the remaining sustained response was inhibited by the addition of 2-amino-5-phosphonopentanoic acid (AP5, 20 mu M), a selective N-methyl-D-aspartate (NMDA) receptor antagonist. Thus the initial peak and the sustained phase of the GABA-evoked [Ca2+](i) increase were mediated by Ca2+ influx through VDCCs and NMDA receptor channels, respectively, and both phases were initiated via the GABA(A) receptor. These results indicate that, in neocortical pyramidal neurons, a reduction in the Cl-gradient converts the GABA(A) receptor-mediated action from nothing or virtually nothing to a large and sustained accumulation of cellular Ca2+. This accumulation is the result of Ca2+ influx mainly through the NMDA receptor channel. Thus GABA(A) normally an inhibitory transmitter, may play an aggravating role in excitotoxicity if a shift in the Cl-equilibrium potential occurs, as reported previously, during cerebral ischemia.
引用
收藏
页码:439 / 446
页数:8
相关论文
共 45 条
[1]   GABA - AN EXCITATORY TRANSMITTER IN EARLY POSTNATAL LIFE [J].
CHERUBINI, E ;
GAIARSA, JL ;
BENARI, Y .
TRENDS IN NEUROSCIENCES, 1991, 14 (12) :515-519
[2]  
CHOI DW, 1990, J NEUROSCI, V10, P2493
[3]  
CONNOR JA, 1987, J NEUROSCI, V7, P1384
[4]   DIFFERENTIAL ONTOGENY OF PRESYNAPTIC AND POSTSYNAPTIC GABA(B) INHIBITION IN RAT SOMATOSENSORY CORTEX [J].
FUKUDA, A ;
MODY, I ;
PRINCE, DA .
JOURNAL OF NEUROPHYSIOLOGY, 1993, 70 (01) :448-452
[5]   NMDA receptor-mediated differential laminar susceptibility to the intracellular Ca2+ accumulation induced by oxygen-glucose deprivation in rat neocortical slices [J].
Fukuda, A ;
Muramatsu, K ;
Okabe, A ;
Shimano, Y ;
Hida, H ;
Fujimoto, I ;
Nishino, H .
JOURNAL OF NEUROPHYSIOLOGY, 1998, 79 (01) :430-438
[6]  
Fukuda A., 1996, Society for Neuroscience Abstracts, V22, P2152
[7]   UNEVEN DISTRIBUTION OF INTRACELLULAR CL- IN RAT HIPPOCAMPAL-NEURONS [J].
HARA, M ;
INOUE, M ;
YASUKURA, T ;
OHNISHI, S ;
MIKAMI, Y ;
INAGAKI, C .
NEUROSCIENCE LETTERS, 1992, 143 (1-2) :135-138
[8]   DISSOCIATION OF SYNCHRONIZATION AND EXCITABILITY IN FUROSEMIDE BLOCKADE OF EPILEPTIFORM ACTIVITY [J].
HOCHMAN, DW ;
BARABAN, SC ;
OWENS, JWM ;
SCHWARTZKROIN, PA .
SCIENCE, 1995, 270 (5233) :99-102
[9]   Role of chloride-homeostasis in the inhibitory control of neuronal network oscillators [J].
Jarolimek, W ;
Brunner, H ;
Lewen, A ;
Misgeld, U .
JOURNAL OF NEUROPHYSIOLOGY, 1996, 75 (06) :2654-2657
[10]   NEUROTRANSMITTERS AND VULNERABILITY OF THE DEVELOPING BRAIN [J].
JOHNSTON, MV .
BRAIN & DEVELOPMENT, 1995, 17 (05) :301-306