DOI: 10.1126/science.2452481. Sustained Dendritic Gradients of Ca <sup>2+</sup> Induced by Excitatory Amino Acids in CA1 Hippocampal Neurons

Sustained Dendritic Gradients of Ca 2+ Induced by Excitatory Amino Acids in CA1 Hippocampal Neurons

10.1126/science.2452481

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Spatially resolved measurements of intracellular free calcium and of the changes produced by excitatory amino acids were made in neurons isolated from adult mammalian brain. Extremely long-lasting (minutes) Ca 2+ gradients were induced in the apical dendrites of hippocampal CA1 neurons after brief (1 to 3 seconds), local application of either glutamate or N -methyl-D-aspartate (NMDA). These gradients reflect the continuous flux of Ca 2+ into the dendrite. The sustained gradients, but not the immediate transient response to the agonists, were prevented by prior treatment with the protein kinase C inhibitor sphingosine. Expression of the long-lasting Ca 2+ gradients generally required a priming or conditioning stimulus with the excitatory agonist. The findings demonstrate a coupling between NMDA receptor activation and long-lasting intracellular Ca 2+ elevation that could contribute to certain use-dependent modifications of synaptic responses in hippocampal CA1 neurons.

Bibliography

Connor, J. A., Wadman, W. J., Hockberger, P. E., & Wong, R. K. S. (1988). Sustained Dendritic Gradients of Ca 2+ Induced by Excitatory Amino Acids in CA1 Hippocampal Neurons. Science, 240(4852), 649â653.

Authors 4

John A. Connor (first)
Wytse J. Wadman (additional)
Philip E. Hockberger (additional)
Robert K. S. Wong (additional)

References 43 Referenced 241

10.1126/science.3003904
ARMSTRONG, D, VOLTAGE-ACTIVATED CALCIUM CHANNELS THAT MUST BE PHOSPHORYLATED TO RESPOND TO MEMBRANE DEPOLARIZATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 84: 2518 (1987). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1987)
BAINBRIDGE, K.G., BRAIN RES 221: 299 (1981). (10.1016/0006-8993(81)90779-4) / BRAIN RES (1981)
BARABAN, J.M., PROTEIN KINASE-C REGULATES IONIC CONDUCTANCE IN HIPPOCAMPAL PYRAMIDAL NEURONS - ELECTROPHYSIOLOGICAL EFFECTS OF PHORBOL ESTERS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 2538 (1985). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1985)
Barrionuevo, G., Proceedings of the National Academy of Sciences of the United States of America 80: 7347 (1983). / Proceedings of the National Academy of Sciences of the United States of America (1983)
10.1113/jphysiol.1986.sp016193
10.1113/jphysiol.1973.sp010273
COHAN, C.S., ELECTRICALLY AND CHEMICALLY MEDIATED INCREASES IN INTRACELLULAR CALCIUM IN NEURONAL GROWTH CONES, JOURNAL OF NEUROSCIENCE 7: 3588 (1987). (10.1523/JNEUROSCI.07-11-03588.1987) / JOURNAL OF NEUROSCIENCE (1987)
COLLINDRIDGE, G.L., TRENDS NEUROSCI 8: 407 (1985). / TRENDS NEUROSCI (1985)
CONNOR, J.A., SPATIALLY RESOLVED CYTOSOLIC CALCIUM RESPONSE TO ANGIOTENSIN-II AND POTASSIUM IN RAT GLOMERULOSA CELLS MEASURED BY DIGITAL IMAGING TECHNIQUES, JOURNAL OF BIOLOGICAL CHEMISTRY 262: 2919 (1987). (10.1016/S0021-9258(18)61595-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1987)
CONNOR, J.A., DEPOLARIZATION-INDUCED AND TRANSMITTER-INDUCED CHANGES IN INTRACELLULAR CA-2+ OF RAT CEREBELLAR GRANULE CELLS IN EXPLANT CULTURES, JOURNAL OF NEUROSCIENCE 7: 1384 (1987). (10.1523/JNEUROSCI.07-05-01384.1987) / JOURNAL OF NEUROSCIENCE (1987)
CONNOR, J.A., DIGITAL IMAGING OF FREE CALCIUM CHANGES AND OF SPATIAL GRADIENTS IN GROWING PROCESSES IN SINGLE, MAMMALIAN CENTRAL-NERVOUS-SYSTEM CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 6179 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
COUSSENS, L, ALTERNATIVE SPLICING INCREASES THE DIVERSITY OF THE HUMAN PROTEIN-KINASE-C FAMILY, DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY 6: 389 (1987). / DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY (1987)
DERIEMER, S.A., ENHANCEMENT OF CALCIUM CURRENT IN APLYSIA NEURONS BY PHORBOL ESTER AND PROTEIN KINASE-C, NATURE 313: 313 (1985). (10.1038/313313a0) / NATURE (1985)
DISTERHOFT, J.F., CONDITIONING-SPECIFIC MEMBRANE-CHANGES OF RABBIT HIPPOCAMPAL-NEURONS MEASURED INVITRO, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 2733 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
10.1016/S0021-9258(19)83641-4
HANNUN, Y.A., SPHINGOSINE INHIBITION OF PROTEIN-KINASE-C ACTIVITY AND OF PHORBOL DIBUTYRATE BINDING INVITRO AND IN HUMAN-PLATELETS, JOURNAL OF BIOLOGICAL CHEMISTRY 261: 12604 (1986). (10.1016/S0021-9258(18)67133-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1986)
HU, G.Y., PROTEIN-KINASE-C INJECTION INTO HIPPOCAMPAL PYRAMIDAL CELLS ELICITS FEATURES OF LONG-TERM POTENTIATION, NATURE 328: 426 (1987). (10.1038/328426a0) / NATURE (1987)
JAHR, C.E., GLUTAMATE ACTIVATES MULTIPLE SINGLE CHANNEL CONDUCTANCES IN HIPPOCAMPAL-NEURONS, NATURE 325: 522 (1987). (10.1038/325522a0) / NATURE (1987)
KAY, A.R., INTRACELLULAR FLUORIDE ALTERS THE KINETIC-PROPERTIES OF CALCIUM CURRENTS FACILITATING THE INVESTIGATION OF SYNAPTIC EVENTS IN HIPPOCAMPAL-NEURONS, JOURNAL OF NEUROSCIENCE 6: 2915 (1986). (10.1523/JNEUROSCI.06-10-02915.1986) / JOURNAL OF NEUROSCIENCE (1986)
KAY, A.R., ISOLATION OF NEURONS SUITABLE FOR PATCH-CLAMPING FROM ADULT MAMMALIAN CENTRAL NERVOUS SYSTEMS, JOURNAL OF NEUROSCIENCE METHODS 16: 227 (1986). (10.1016/0165-0270(86)90040-3) / JOURNAL OF NEUROSCIENCE METHODS (1986)
KAY, A.R., CALCIUM CURRENT ACTIVATION KINETICS IN ISOLATED PYRAMIDAL NEURONS OF THE CA1 REGION OF THE MATURE GUINEA-PIG HIPPOCAMPUS, JOURNAL OF PHYSIOLOGY-LONDON 392: 603 (1987). (10.1113/jphysiol.1987.sp016799) / JOURNAL OF PHYSIOLOGY-LONDON (1987)
10.1038/305719a0
10.1126/science.6144182
10.1038/321519a0
MALENKA, R.C., PHORBOL ESTERS MIMIC SOME CHOLINERGIC ACTIONS IN HIPPOCAMPAL PYRAMIDAL NEURONS, JOURNAL OF NEUROSCIENCE 6: 475 (1986). (10.1523/JNEUROSCI.06-02-00475.1986) / JOURNAL OF NEUROSCIENCE (1986)
10.1038/321175a0
MELCHERS, BPC, DIFFERENTIAL-EFFECTS OF ELEVATED EXTRACELLULAR CALCIUM CONCENTRATIONS ON FIELD POTENTIALS IN DENTATE GYRUS AND CA1 OF THE RAT HIPPOCAMPAL SLICE PREPARATION, NEUROSCIENCE LETTERS 77: 37 (1987). (10.1016/0304-3940(87)90603-3) / NEUROSCIENCE LETTERS (1987)
NUMANN, R.E., OUTWARD CURRENTS OF SINGLE HIPPOCAMPAL CELLS OBTAINED FROM THE ADULT GUINEA-PIG, JOURNAL OF PHYSIOLOGY-LONDON 393: 331 (1987). (10.1113/jphysiol.1987.sp016826) / JOURNAL OF PHYSIOLOGY-LONDON (1987)
NUMANN, R.E., VOLTAGE-CLAMP STUDY ON GABA RESPONSE DESENSITIZATION IN SINGLE PYRAMIDAL CELLS DISSOCIATED FROM THE HIPPOCAMPUS OF ADULT GUINEA-PIGS, NEUROSCIENCE LETTERS 47: 289 (1984). (10.1016/0304-3940(84)90528-7) / NEUROSCIENCE LETTERS (1984)
REUTER, H, CALCIUM-CHANNEL MODULATION BY NEUROTRANSMITTERS, ENZYMES AND DRUGS, NATURE 301: 569 (1983). (10.1038/301569a0) / NATURE (1983)
SCHWARTZKROIN, P.A., PROBABLE CALCIUM SPIKES IN HIPPOCAMPAL NEURONS, BRAIN RESEARCH 135: 157 (1977). (10.1016/0006-8993(77)91060-5) / BRAIN RESEARCH (1977)
STRONG, J.A., STIMULATION OF PROTEIN-KINASE-C RECRUITS COVERT CALCIUM CHANNELS IN APLYSIA BAG CELL NEURONS, NATURE 325: 714 (1987). (10.1038/325714a0) / NATURE (1987)
TEYLER, T.J., LONG-TERM POTENTIATION, ANNUAL REVIEW OF NEUROSCIENCE 10: 131 (1987). (10.1146/annurev.ne.10.030187.001023) / ANNUAL REVIEW OF NEUROSCIENCE (1987)
TSIEN, R.W., MECHANISMS OF CALCIUM-CHANNEL MODULATION BY BETA-ADRENERGIC AGENTS AND DIHYDROPYRIDINE CALCIUM AGONISTS, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 18: 691 (1986). (10.1016/S0022-2828(86)80941-5) / JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY (1986)
TSIEN, R.Y., FLUORESCENCE RATIO IMAGING - A NEW WINDOW INTO INTRACELLULAR IONIC SIGNALING, TRENDS IN BIOCHEMICAL SCIENCES 11: 450 (1986). (10.1016/0968-0004(86)90245-8) / TRENDS IN BIOCHEMICAL SCIENCES (1986)
TURNER, R.W., CALCIUM-INDUCED LONG-TERM POTENTIATION IN THE HIPPOCAMPUS, NEUROSCIENCE 7: 1411 (1982). (10.1016/0306-4522(82)90254-8) / NEUROSCIENCE (1982)
WADMAN, W.J., HIPPOCAMPAL SLICES OF KINDLED RATS REVEAL CALCIUM INVOLVEMENT IN EPILEPTOGENESIS, EXPERIMENTAL BRAIN RESEARCH 57: 404 (1985). / EXPERIMENTAL BRAIN RESEARCH (1985)
WHITE, W.F., GLUTAMATE AS TRANSMITTER OF HIPPOCAMPAL PERFORANT PATH, NATURE 270: 356 (1977). (10.1038/270356a0) / NATURE (1977)
WIGSTROM, H, CALCIUM DEPENDENCY OF SYNAPTIC LONG-LASTING POTENTIATION IN THE HIPPOCAMPAL SLICE, ACTA PHYSIOLOGICA SCANDINAVICA 105: 126 (1979). (10.1111/j.1748-1716.1979.tb06323.x) / ACTA PHYSIOLOGICA SCANDINAVICA (1979)
10.1038/318558a0
WILSON, E, INHIBITION OF THE OXIDATIVE BURST IN HUMAN-NEUTROPHILS BY SPHINGOID LONG-CHAIN BASES - ROLE OF PROTEIN-KINASE-C IN ACTIVATION OF THE BURST, JOURNAL OF BIOLOGICAL CHEMISTRY 261: 12616 (1986). (10.1016/S0021-9258(18)67135-2) / JOURNAL OF BIOLOGICAL CHEMISTRY (1986)
WONG, RKS, INTRA-DENDRITIC RECORDINGS FROM HIPPOCAMPAL NEURONS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76: 986 (1979). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1979)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 5:21 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 11:10 a.m.)
Indexed	3 months ago (May 20, 2025, 9:31 a.m.)
Issued	37 years, 3 months ago (April 29, 1988)
Published	37 years, 3 months ago (April 29, 1988)
Published Print	37 years, 3 months ago (April 29, 1988)

Funders 0

None

BibTeX

@article{Connor_1988, title={Sustained Dendritic Gradients of Ca 2+ Induced by Excitatory Amino Acids in CA1 Hippocampal Neurons}, volume={240}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2452481}, DOI={10.1126/science.2452481}, number={4852}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Connor, John A. and Wadman, Wytse J. and Hockberger, Philip E. and Wong, Robert K. S.}, year={1988}, month=apr, pages={649–653} }

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