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Age-dependent decrease in TRPM4 channel expression but not trafficking alters urinary bladder smooth muscle

Sarah E Maxwell1, M Dennis Leo1, John Malysz1

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA.

Physiological Reports
|February 24, 2021
PubMed
Summary
This summary is machine-generated.

Urinary bladder smooth muscle (UBSM) function changes with age due to altered TRPM4 channel expression. Adult guinea pigs show reduced TRPM4 protein, impacting muscle contractions and highlighting age-related physiological shifts.

Keywords:
Western blotchannel traffickingdetrusorion channelmaturation

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Area of Science:

  • Physiology
  • Urology
  • Ion Channel Biology

Background:

  • Urinary bladder smooth muscle (UBSM) ion channel function is crucial for micturition and can change with age.
  • Transient Receptor Potential Melastatin-4 (TRPM4) channels play a significant role in UBSM physiology.
  • The age-dependent expression and function of TRPM4 channels in UBSM remain largely uncharacterized.

Purpose of the Study:

  • To investigate the changes in TRPM4 channel protein expression and function in UBSM from juvenile and adult male guinea pigs.
  • To determine the impact of age on TRPM4 channel trafficking and its role in UBSM contractility.

Main Methods:

  • Western blot analysis was used to quantify TRPM4 channel protein expression in UBSM from juvenile and adult guinea pigs.
  • The effects of TRPM4 channel inhibitors (9-phenanthrol and glibenclamide) on spontaneous and KCl-induced phasic contractions of isolated UBSM strips were assessed.
  • Cell surface and intracellular TRPM4 protein localization was examined to evaluate channel trafficking.

Main Results:

  • Adult UBSM exhibited a 50-70% reduction in total TRPM4 protein expression compared to juvenile UBSM.
  • TRPM4 inhibition with 9-phenanthrol demonstrated lower potency and efficacy in adult UBSM, correlating with reduced protein levels.
  • Channel trafficking to the cell surface remained preserved in both age groups, with approximately 80% of TRPM4 located at the cell surface.

Conclusions:

  • TRPM4 channel expression and function in UBSM significantly decrease with age in male guinea pigs.
  • Age-related changes in TRPM4 expression impact UBSM contractility, suggesting a role in age-associated alterations in bladder function.
  • Preserved channel trafficking mechanisms indicate that reduced expression, rather than impaired trafficking, is the primary factor in age-related functional changes.