DEVELOPMENTAL-CHANGES IN INTRACELLULAR CALCIUM REGULATION IN RAT CEREBRAL-CORTEX DURING HYPOXIA

被引:65
作者
BICKLER, PE
GALLEGO, SM
HANSEN, BM
机构
[1] Department of Anesthesia, University of California, San Francisco, CA
[2] Department of Anesthesia, Health Sciences East 1386, Univ. of California Medical Center, San Francisco
关键词
ADENOSINE TRIPHOSPHATE; ANOXIA; BRAIN SLICES; FURA-2; IONIC REGULATION; NEONATAL RATS;
D O I
10.1038/jcbfm.1993.103
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
During the first weeks of life, injury to the central nervous system caused by brief periods of oxygen deprivation greatly increases. To investigate possible causes for this change, the effects of hypoxia or application of the excitatory neurotransmitter glutamate on intracellular calcium ([Ca2+]i) and ATP were studied in rat cerebrocortical brain slices. [Ca2+]i was measured fluorometrically with the indicator Fura-2. Hypoxia (95% N2/5% CO2) or 100 muM sodium cyanide produced gradual elevations in [Ca2+]i and ATP depletion in slices from rats <2 weeks old, but rapid changes in older rats. After 20 min, [Ca2+]i in adult slices exposed to cyanide was 1,980 +/- 3 10 nM; in day 1-14 animals, it was 7% +/- 181 nM (p < 0.05). Combination of cyanide and a glycolytic inhibitor (iodoacetate) rapidly elevated [Ca2+]i and depleted ATP in all age groups. Energy utilization during anoxia, assessed by measuring ATP fall in cyanide/iodoacetate-treated brain slices, increased with age. Elevations in [Ca2+]i caused by application of 500 muM glutamate increased 240% from days 1-2 to day 28, but ATP loss caused by glutamate did not change with age. The N-methYl-D-aspartate antagonist MK-801 delayed calcium entry during the initial 5-7 min of hypoxia or cyanide in rats <2 weeks old. We conclude that anaerobic ATP production, conservation of energy by reduced ATP consumption, and reduced sensitivity to glutamate contribute to delaying elevation in [Ca2+]i in neonatal rat brain during hypoxia.
引用
收藏
页码:811 / 819
页数:9
相关论文
共 24 条
[1]   TOLERANCE TO COLD AND ANOXIA IN INFANT RATS [J].
ADOLPH, EF .
AMERICAN JOURNAL OF PHYSIOLOGY, 1948, 155 (03) :366-377
[2]  
BEAR MF, 1990, J NEUROSCI, V10, P909
[3]   CHANGES IN MESSENGER-RNAS CODING FOR NEUROTRANSMITTER RECEPTORS AND VOLTAGE-OPERATED CHANNELS IN THE DEVELOPING RAT CEREBRAL-CORTEX [J].
CARPENTER, MK ;
PARKER, I ;
MILEDI, R .
DEVELOPMENTAL BIOLOGY, 1990, 138 (02) :313-323
[5]   CARBOHYDRATE AND ENERGY METABOLISM IN PERINATAL RAT-BRAIN - RELATION TO SURVIVAL IN ANOXIA [J].
DUFFY, TE ;
KOHLE, SJ ;
VANNUCCI, RC .
JOURNAL OF NEUROCHEMISTRY, 1975, 24 (02) :271-276
[6]   Tolerance of the newborn to anoxia [J].
Fazekas, JF ;
Alexander, FAD ;
Himwich, HE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1941, 134 (02) :0281-0287
[7]   O-2 DEPRIVATION INDUCES A MAJOR DEPOLARIZATION IN BRAIN-STEM NEURONS IN THE ADULT BUT NOT IN THE NEONATAL RAT [J].
HADDAD, GG ;
DONNELLY, DF .
JOURNAL OF PHYSIOLOGY-LONDON, 1990, 429 :411-428
[8]   EFFECT OF ANOXIA ON ION DISTRIBUTION IN THE BRAIN [J].
HANSEN, AJ .
PHYSIOLOGICAL REVIEWS, 1985, 65 (01) :101-148
[9]   EXTRACELLULAR POTASSIUM CONCENTRATION IN JUVENILE AND ADULT RAT-BRAIN CORTEX DURING ANOXIA [J].
HANSEN, AJ .
ACTA PHYSIOLOGICA SCANDINAVICA, 1977, 99 (04) :412-420
[10]   DEVELOPMENTAL REGULATION OF NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS AT A CENTRAL SYNAPSE [J].
HESTRIN, S .
NATURE, 1992, 357 (6380) :686-689