Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol

Shankar P. Parajuli, Kiril L. Hristov, Michelle N. Sullivan, Wenkuan Xin, Amy C. Smith, Scott Earley, John Malysz, Georgi Petkov

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel has been recently identified in detrusor smooth muscle (DSM) of the urinary bladder. Two recent publications by our research group provide evidence in support of the novel hypothesis that TRPM4 channels enhance DSM excitability and contractility. This is a critical question as prior studies have primarily targeted hyperpolarizing currents facilitated by K+ channels, but the depolarizing component in DSM cells is not well understood. For the first time, we utilized the selective TRPM4 channel inhibitor, 9-phenanthrol, to investigate TRPM4 channel functional effects in DSM at both cellular and tissue levels in rodents. Our new data presented here showed that in rat DSM cells, 9-phenanthrol attenuates spontaneous inward currents stimulated with muscarinic receptor agonist, carbachol, thus reducing DSM cell excitability. In support of our original hypothesis, we found that TRPM4 channel mRNA levels are much higher in DSM vs. vascular smooth muscle and that inhibition of TRPM4 channels can potentially attenuate DSM excitability. Thus, we postulate the novel concept that selective pharmacological inhibition of TRPM4 channels can limit both excitability and contractility of DSM.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalChannels
Volume7
Issue number6
DOIs
StatePublished - Jan 1 2013

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Modulators
Smooth Muscle
Muscle
Urinary Bladder
Smooth Muscle Myocytes
Muscarinic Agonists
Monovalent Cations
Carbachol
Muscarinic Receptors
Vascular Smooth Muscle
9-phenanthrol
Rodentia
Messenger RNA
Rats
Research
Tissue

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

Cite this

Parajuli, S. P., Hristov, K. L., Sullivan, M. N., Xin, W., Smith, A. C., Earley, S., ... Petkov, G. (2013). Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol. Channels, 7(6), 1-5. https://doi.org/10.4161/chan.26289

Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol. / Parajuli, Shankar P.; Hristov, Kiril L.; Sullivan, Michelle N.; Xin, Wenkuan; Smith, Amy C.; Earley, Scott; Malysz, John; Petkov, Georgi.

In: Channels, Vol. 7, No. 6, 01.01.2013, p. 1-5.

Research output: Contribution to journalArticle

Parajuli, SP, Hristov, KL, Sullivan, MN, Xin, W, Smith, AC, Earley, S, Malysz, J & Petkov, G 2013, 'Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol', Channels, vol. 7, no. 6, pp. 1-5. https://doi.org/10.4161/chan.26289
Parajuli SP, Hristov KL, Sullivan MN, Xin W, Smith AC, Earley S et al. Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol. Channels. 2013 Jan 1;7(6):1-5. https://doi.org/10.4161/chan.26289
Parajuli, Shankar P. ; Hristov, Kiril L. ; Sullivan, Michelle N. ; Xin, Wenkuan ; Smith, Amy C. ; Earley, Scott ; Malysz, John ; Petkov, Georgi. / Control of urinary bladder smooth muscle excitability by the TRPM4 channel modulator 9-phenanthrol. In: Channels. 2013 ; Vol. 7, No. 6. pp. 1-5.
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