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Membrane composition modulates prestin-associated charge movement.

John Sfondouris1, Lavanya Rajagopalan, Fred A Pereira

  • 1Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.

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Membrane cholesterol and docosahexaenoic acid significantly impact outer hair cell (OHC) function by altering prestin protein activity. This research quantifies how these lipids affect OHC electromotility, crucial for hearing.

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Area of Science:

  • Auditory Neuroscience
  • Cellular Biophysics
  • Membrane Biology

Background:

  • Outer hair cells (OHCs) are vital for hearing, employing electromotility for signal amplification.
  • The OHC membrane protein prestin drives this motor function.
  • Previous studies linked membrane cholesterol to prestin's nonlinear capacitance.

Purpose of the Study:

  • To investigate how membrane cholesterol and docosahexaenoic acid (DHA) affect prestin-associated charge movement.
  • To quantify the relationship between membrane lipid composition and prestin function in a human embryonic kidney (HEK 293) cell model.

Main Methods:

  • Utilized a HEK 293 cell model expressing prestin.
  • Manipulated membrane cholesterol and DHA levels.
  • Measured prestin-associated nonlinear capacitance and charge movement.

Main Results:

  • Increased membrane cholesterol caused a hyperpolarizing shift in peak voltage (Vpkc) and decreased charge movement, linearly dependent on concentration.
  • Cholesterol depletion shifted Vpkc depolarizingly but did not alter charge movement magnitude.
  • Increased DHA resulted in a hyperpolarizing Vpkc shift and increased charge movement.

Conclusions:

  • Membrane lipid composition, specifically cholesterol and DHA, directly modulates prestin's voltage-dependent activity and charge movement.
  • These findings provide quantitative insights into how membrane properties fine-tune OHC electromotility for auditory function.