Physiological evidence that pyramidal neurons lack functional water channels

R. David Andrew, Mark W. Labron, Susan E. Boehnke, Lisa Carnduff, Sergei A. Kirov

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The physiological conditions that swell mammalian neurons are clinically important but contentious. Distinguishing the neuronal component of brain swelling requires viewing intact neuronal cell bodies, dendrites, and axons and measuring their changing volume in real time. Cultured or dissociated neuronal somata swell within minutes under acutely overhydrated conditions and shrink when strongly dehydrated. But paradoxically, most central nervous system (CNS) neurons do not express aquaporins, the membrane channels that conduct osmotically driven water. Using 2-photon laser scanning microscopy (2PLSM), we monitored neuronal volume under osmotic stress in real time. Specifically, the volume of pyramidal neurons in cerebral cortex and axon terminals comprising cerebellar mossy fibers was measured deep within live brain slices. The expected swelling or shrinking of the gray matter was confirmed by recording altered light transmittance and by indirectly measuring extracellular resistance over a wide osmotic range of -80 to +80 milliOsmoles (mOsm). Neurons expressing green fluorescent protein were then imaged with 2PLSM between -40 and +80 mOsm over 20 min. Surprisingly, pyramidal somata, dendrites, and spines steadfastly maintained their volume, as did the cerebellar axon terminals. This precluded a need for the neurons to acutely regulate volume, preserved their intrinsic electrophysiological stability, and confirmed that these CNS nerve cells lack functional aquaporins. Thus, whereas water easily permeates the aquaporin-rich endothelia and glia driving osmotic brain swelling, neurons tenatiously maintain their volume. However, these same neurons then swell dramatically upon oxygen/glucose deprivation or [K+]0 elevation, so prolonged depolarization (as during stroke or seizure) apparently swells neurons by opening nonaquaporin channels to water.

Original languageEnglish (US)
Pages (from-to)787-802
Number of pages16
JournalCerebral Cortex
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2007

Fingerprint

Aquaporins
Pyramidal Cells
Neurons
Brain Edema
Presynaptic Terminals
Carisoprodol
Dendrites
Photons
Confocal Microscopy
Central Nervous System
Water
Osmotic Pressure
Green Fluorescent Proteins
Ion Channels
Nerve Fibers
Neuroglia
Cerebral Cortex
Endothelium
Axons
Seizures

Keywords

  • 2-photon microscopy
  • Anoxic depolarization
  • Aquaporins
  • Barrier membrane
  • Dendritic beading
  • Green fluorescent protein
  • Intrinsic optical signals
  • Ischemia
  • Light transmittance
  • Osmolality
  • Oxygen/glucose deprivation
  • Volume regulation

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Physiological evidence that pyramidal neurons lack functional water channels. / Andrew, R. David; Labron, Mark W.; Boehnke, Susan E.; Carnduff, Lisa; Kirov, Sergei A.

In: Cerebral Cortex, Vol. 17, No. 4, 01.04.2007, p. 787-802.

Research output: Contribution to journalArticle

Andrew, R. David ; Labron, Mark W. ; Boehnke, Susan E. ; Carnduff, Lisa ; Kirov, Sergei A. / Physiological evidence that pyramidal neurons lack functional water channels. In: Cerebral Cortex. 2007 ; Vol. 17, No. 4. pp. 787-802.
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