TRPM4 channel: a new player in urinary bladder smooth muscle function in rats
Amy C Smith1, Shankar P Parajuli, Kiril L Hristov
1Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, Columbia, SC 29208, USA.
American Journal of Physiology. Renal Physiology
|January 4, 2013
Summary
Transient Receptor Potential Melastatin 4 (TRPM4) channels are present in rat detrusor smooth muscle (DSM) and regulate its excitability and contractility. Inhibiting TRPM4 reduces intracellular calcium and smooth muscle contractions.
Area of Science:
- Physiology
- Molecular Biology
- Pharmacology
Background:
- Transient Receptor Potential Melastatin 4 (TRPM4) channels are Ca(2+)-activated, monovalent cation channels involved in various cellular processes.
- Their role in detrusor smooth muscle (DSM) excitability and contractility remains unexplored.
Purpose of the Study:
- To investigate the expression and function of TRPM4 channels in rat detrusor smooth muscle.
- To determine if TRPM4 channels play a role in regulating DSM contractility.
Main Methods:
- RT-PCR, Western blotting, immunohistochemistry, and immunocytochemistry were used to detect TRPM4 expression at mRNA and protein levels.
- Perforated patch-clamp recordings assessed electrophysiological properties.
- Live-cell Ca(2+) imaging and isometric tension recordings evaluated DSM function.
Main Results:
- TRPM4 channels were detected in rat DSM at both mRNA and protein levels.
- Inhibition of TRPM4 channels with 9-hydroxyphenanthrene (9-phenanthrol) reduced spontaneous inward currents and intracellular Ca(2+) levels.
- TRPM4 inhibition significantly decreased spontaneous, pharmacologically induced, and electrically stimulated DSM contractions.
Conclusions:
- This study provides the first evidence for the presence and function of TRPM4 channels in rat detrusor smooth muscle.
- TRPM4 channels are critical regulators of rat DSM excitability and contractility.
