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The Journal of Neurophysiology Vol. 82 No. 4 October 1999, pp. 1818-1831
Copyright ©1999 by the American Physiological Society
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710
Müller, Michael and
George G. Somjen.
Intrinsic Optical Signals in Rat Hippocampal Slices During
Hypoxia-Induced Spreading Depression-Like Depolarization. J. Neurophysiol. 82: 1818-1831, 1999. In
interfaced rat hippocampal slices spreading depression (SD) and
hypoxia-induced SD-like depolarization are associated with increased
light reflectance and decreased light transmittance, indicating
increased light scattering. By contrast, mild hypotonicity or
electrical stimulation decrease light scattering, which is usually
taken to be caused by cell swelling. This difference has been
attributed to experimental conditions, but in our laboratory moderate
osmotic challenge and SD produced opposite intrinsic optical signals
(IOSs) in the same slice under identical conditions. To decide whether
the SD-induced IOS is related to cell swelling, we investigated the
effects of Cl
transport inhibitors and Cl
withdrawal on both light reflectance and transmittance, as well as on
changes in interstitial volume and tissue electrical resistance. In
normal [Cl]o, early during hypoxia, there
was a slight decrease in light reflectance paired with increase in
transmittance. At the onset of hypoxic SD, coincident with the onset of
cell swelling (restriction of TMA+ space), the IOS signals
suddenly inverted, indicating sharply increased scattering. The
SD-related IOSs started in a single spot and spread out over the entire
CA1 region without invading CA3. Application of 2 mM furosemide
decreased IOS intensity. When [Cl]o was
substituted by methylsulfate or gluconate, the SD-related reflectance
increase and transmittance decrease were suppressed and replaced by
opposite signals, indicating scattering decrease. Yet Cl
withdrawal did not prevent cell swelling measured as shrinkage of
TMA+ space. The SD-related increase of tissue electrical
resistance was reduced when bath Cl was replaced by
methylsulfate and almost eliminated when replaced by gluconate. The
TMA+ signal is judged to be a more reliable indicator of
interstitial space than tissue resistance. Neither application of
cyclosporin A nor raising [Mg2+]o depressed
the SD-related reflectance increase, suggesting that Cl
flux through mitochondrial "megachannels" may not be a major factor
in its generation. Fluoroacetate poisoning of glial cells (5 mM)
accelerated SD onset and enhanced the SD-induced reflectance increase
threefold. This suggests, first, that glial cells normally moderate the
SD process and, second, that neurons are the predominant generators of
the light-scattering increase. We conclude that light scattering by
cerebral tissue can be changed by at least two different physical
processes. Cell swelling decreases light scattering, whereas a second
process increases scattering. During hypoxic SD the scattering increase
masks the swelling-induced scattering decrease, but the latter is
revealed when Cl is removed. The scattering increase is
Cl dependent, nevertheless it is apparently not related
to cell volume changes. Its underlying mechanism is as yet not clear; possible factors are discussed.
This article has been cited by other articles:
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  F. Funke, M. Kron, M. Dutschmann, and M. Muller Infant Brain Stem Is Prone to the Generation of Spreading Depression During Severe Hypoxia J Neurophysiol, May 1, 2009; 101(5): 2395 - 2410. [Abstract] [Full Text] [PDF]
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M. Fischer, J. Reuter, F. J. Gerich, B. Hildebrandt, S. Hagele, D. Katschinski, and M. Muller Enhanced Hypoxia Susceptibility in Hippocampal Slices From a Mouse Model of Rett Syndrome J Neurophysiol, February 1, 2009; 101(2): 1016 - 1032. [Abstract] [Full Text] [PDF]
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F. J. Gerich, S. Hepp, I. Probst, and M. Muller Mitochondrial Inhibition Prior to Oxygen-Withdrawal Facilitates the Occurrence of Hypoxia-Induced Spreading Depression in Rat Hippocampal Slices J Neurophysiol, July 1, 2006; 96(1): 492 - 504. [Abstract] [Full Text] [PDF]
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M. Muller and K. Ballanyi Dynamic Recording of Cell Death in the In Vitro Dorsal Vagal Nucleus of Rats in Response to Metabolic Arrest J Neurophysiol, January 1, 2003; 89(1): 551 - 561. [Abstract] [Full Text] [PDF]
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T. R. Anderson and R. D. Andrew Spreading Depression: Imaging and Blockade in the Rat Neocortical Brain Slice J Neurophysiol, November 1, 2002; 88(5): 2713 - 2725. [Abstract] [Full Text] [PDF]
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A. M. Ba, M. Guiou, N. Pouratian, A. Muthialu, D. E. Rex, A. F. Cannestra, J. W. Y. Chen, and A. W. Toga Multiwavelength Optical Intrinsic Signal Imaging of Cortical Spreading Depression J Neurophysiol, November 1, 2002; 88(5): 2726 - 2735. [Abstract] [Full Text] [PDF]
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D. Fayuk, P. G. Aitken, G. G. Somjen, and D. A. Turner Two Different Mechanisms Underlie Reversible, Intrinsic Optical Signals in Rat Hippocampal Slices J Neurophysiol, April 1, 2002; 87(4): 1924 - 1937. [Abstract] [Full Text] [PDF]
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M. Haller, S. L. Mironov, and D. W. Richter Intrinsic Optical Signals in Respiratory Brain Stem Regions of Mice: Neurotransmitters, Neuromodulators, and Metabolic Stress J Neurophysiol, July 1, 2001; 86(1): 412 - 421. [Abstract] [Full Text] [PDF]
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 G. G. Somjen Mechanisms of Spreading Depression and Hypoxic Spreading Depression-Like Depolarization Physiol Rev, July 1, 2001; 81(3): 1065 - 1096. [Abstract] [Full Text] [PDF]
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M. Muller and G. G. Somjen Na+ Dependence and the Role of Glutamate Receptors and Na+ Channels in Ion Fluxes During Hypoxia of Rat Hippocampal Slices J Neurophysiol, October 1, 2000; 84(4): 1869 - 1880. [Abstract] [Full Text] [PDF]
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S. Bahar, D. Fayuk, G. G. Somjen, P. G. Aitken, and D. A. Turner Mitochondrial and Intrinsic Optical Signals Imaged During Hypoxia and Spreading Depression in Rat Hippocampal Slices J Neurophysiol, July 1, 2000; 84(1): 311 - 324. [Abstract] [Full Text] [PDF]
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M. Muller and G. G. Somjen Na+ and K+ Concentrations, Extra- and Intracellular Voltages, and the Effect of TTX in Hypoxic Rat Hippocampal Slices J Neurophysiol, February 1, 2000; 83(2): 735 - 745. [Abstract] [Full Text] [PDF]
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