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Updated: Jan 1, 2026

Preparation and Utilization of Freshly Isolated Human Detrusor Smooth Muscle Cells for Characterization of 9-Phenanthrol-Sensitive Cation Currents
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TRPM4 channel inhibitors 9-phenanthrol and glibenclamide differentially decrease guinea pig detrusor smooth muscle

John Malysz1, Sarah E Maxwell1, Viktor Yarotskyy1

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

American Journal of Physiology. Cell Physiology
|December 19, 2019
PubMed
Summary

Transient receptor potential melastatin-4 (TRPM4) channels influence detrusor smooth muscle (DSM) function. This study found 9-phenanthrol more effective than glibenclamide in modulating DSM excitability and contractility, suggesting SUR-TRPM4 complexes do not impact DSM function.

Keywords:
TRPM4cationcontractilitypatch-clampsmooth muscleurinary bladder

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Area of Science:

  • Physiology
  • Pharmacology
  • Urology

Background:

  • Nonselective cation channels, including transient receptor potential melastatin-4 (TRPM4), are crucial for regulating detrusor smooth muscle (DSM) function.
  • TRPM4 channels can function as homomers or form complexes with sulfonylurea receptors (SURs).

Purpose of the Study:

  • To investigate the roles of TRPM4 and SUR-TRPM4 channels in DSM excitability and contractility.
  • To compare the effects of TRPM4/SUR-TRPM4 channel modulators 9-phenanthrol and glibenclamide on DSM function.

Main Methods:

  • Utilized amphotericin-B perforated patch-clamp electrophysiology on freshly-isolated guinea pig DSM cells.
  • Employed isometric tension recordings on mucosa-free DSM strips to assess contractility.
  • Examined the effects of 9-phenanthrol, glibenclamide, and diazoxide on DSM cell currents and muscle strip contractions.

Main Results:

  • 9-Phenanthrol demonstrated concentration-dependent, voltage-sensitive inhibition of cation currents in DSM cells, more potent than glibenclamide.
  • Glibenclamide showed lower potency and efficacy compared to 9-phenanthrol in attenuating spontaneous and KCl-induced DSM phasic contractions.
  • Diazoxide, a SUR-TRPM4 activator, had minimal effect on cation currents, suggesting SUR-TRPM4 complexes do not significantly contribute to DSM function.

Conclusions:

  • The differential effects of 9-phenanthrol and glibenclamide suggest distinct mechanisms of action on DSM excitability and contractility.
  • The findings indicate that SUR-TRPM4 complexes are unlikely to play a significant role in regulating detrusor smooth muscle function.
  • This research enhances the understanding of the pharmacological actions of 9-phenanthrol and glibenclamide on DSM cation currents.