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Human trabecular meshwork cell volume regulation.

Claire H Mitchell1, Johannes C Fleischhauer, W Daniel Stamer

  • 1Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6085, USA.

American Journal of Physiology. Cell Physiology
|June 11, 2002
PubMed
Summary
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Human trabecular meshwork (TM) cells regulate intraocular pressure. This study reveals that cell volume is controlled by ion transport mechanisms, including Na+/H+ antiports and swelling-activated K+ and Cl- channels, independent of calcium.

Area of Science:

  • Ocular Physiology
  • Cell Biology
  • Biophysics

Background:

  • Trabecular meshwork (TM) cell volume influences aqueous humor outflow and intraocular pressure (IOP).
  • Understanding the ion transport mechanisms regulating TM cell volume is crucial for managing glaucoma and related conditions.

Purpose of the Study:

  • To investigate the roles of Na+/H+ exchange, Cl-/HCO3- exchange, and K+-Cl- efflux in regulating human TM cell volume.
  • To elucidate the specific ion channels and transporters involved in regulatory volume decrease (RVD) and fluid uptake.

Main Methods:

  • Cultured human TM cells were used to study cell volume, chloride currents, and intracellular calcium.
  • Techniques included calcein fluorescence for volume, whole-cell patch clamping for currents, and fura 2 fluorescence for Ca2+ activity.

Related Experiment Videos

  • Specific inhibitors were employed to probe the function of Na+/H+ antiports, K+ channels, Cl- channels, and various symports.

    • Main Results:

    • Na+/H+ exchange significantly impacts isotonic cell volume, particularly at physiological bicarbonate levels.
    • Hypotonicity induces a calcium-independent regulatory volume decrease (RVD) mediated by swelling-activated K+ and Cl- channels.
    • The Na+-K+-2Cl- symport plays a role in fluid uptake under hypotonic conditions, while K+-Cl- symports may also contribute to volume regulation.

    Conclusions:

    • Human TM cells exhibit calcium-independent RVD regulated by specific ion transport systems.
    • Swelling-activated K+ and Cl- channels, Na+/H+ antiports, and potentially K+-Cl- and Na+-K+-2Cl- symports are key regulators of TM cell volume.
    • These findings provide insights into the mechanisms controlling IOP and potential therapeutic targets for ocular diseases.