Role of endogenous ENaC and TRP channels in the myogenic response of rat posterior cerebral arteries

PLoS One. 2013 Dec 31;8(12):e84194. doi: 10.1371/journal.pone.0084194. eCollection 2013.


Aims: Mechanogated ion channels are predicted to mediate pressure-induced myogenic vasoconstriction in small resistance arteries. Recent findings have indicated that transient receptor potential (TRP) channels and epithelial sodium channels (ENaC) are involved in mechanotransduction. The purpose of this study was to investigate the role of TRP channels and ENaC in the myogenic response. Our previous study suggested that ENaC could be a component of the mechanosensitive ion channels in rat posterior cerebral arteries (PCA). However, the specific ion channel proteins mediating myogenic constriction are unknown. Here we found, for the first time, that ENaC interacted with TRPM4 but not with TRPC6 using immunoprecipitation and confocal microscopy.

Methods and results: Treatment with a specific βENaC inhibitor, amiloride, a specific TRPM4 inhibitor, 9-phenanthrol, and a TRPC6 inhibitor, SKF96365, resulted in inhibition of the pressure-induced myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with small interfering RNA of βENaC, TRPM4, and TRPC6. Co-treatment with amiloride and 9-phenanthrol showed a similar inhibitory effect on myogenic contraction compared to single treatment with amiloride or 9-phenanthrol. The myogenic response was not affected by 9-phenanthrol or amiloride treatment in PCA transfected with βENaC or TRPM4 siRNA, respectively. However, pressure-induced myogenic response was fully inhibited by co-treatment with amiloride, 9-phenanthrol, and SKF96365, and by treatment with SKF96365 in PCA transfected with βENaC siRNA.

Conclusion: Our results suggest that ENaC, TRPM4, and TRPC6 play important roles in the pressure-induced myogenic response, and that ENaC and TRPM4 interact in rat PCA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride
  • Animals
  • Blood Pressure / physiology*
  • Epithelial Sodium Channels / metabolism*
  • Hemodynamics / physiology*
  • Imidazoles
  • Phenanthrenes
  • Posterior Cerebral Artery / physiology*
  • RNA, Small Interfering
  • Rats
  • TRPM Cation Channels / metabolism*


  • Epithelial Sodium Channels
  • Imidazoles
  • Phenanthrenes
  • RNA, Small Interfering
  • TRPM Cation Channels
  • TRPM4 protein, rat
  • Amiloride
  • 9-phenanthrol
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole

Grant support

This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0007540). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.