Fenamates block gap junction coupling and potentiate BKCa channels in guinea pig arteriolar cells

Xin Zhi Li, Ke Tao Ma, Bing Cai Guan, Li Li, Lei Zhao, Zhong Shuang Zhang, Jun Qiang Si, Zhi Gen Jiang

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We determined the actions of the fenamates, flufenamic acid (FFA) and niflumic acid (NFA), on gap junction-mediated intercellular coupling between vascular smooth muscle cells (VSMC) in situ of acutely isolated arteriole segments from the three vascular beds: the spiral modiolar artery (SMA), anterior inferior cerebellar artery (AICA) and mesenteric artery (MA), and on non-junctional membrane channels in dispersed VSMCs. Conventional whole-cell recording methods were used. FFA reversibly suppressed the input conductance (Ginput) or increased the input resistance (Rinput) in a concentration dependent manner, with slightly different IC50s for the SMA, AICA and MA segments (26, 33 and 56 μM respectively, P>0.05). Complete electrical isolation of the recorded VSMC was normally reached at ≥300 μM. NFA had a similar effect on gap junction among VSMCs with an IC50 of 40, 48 and 62 μM in SMA, AICA and MA segments, respectively. In dispersed VSMCs, FFA and NFA increased outward rectifier K +-current mediated by the big conductance calcium-activated potassium channel (BKCa) in a concentration-dependent manner, with a similar EC50 of ∼300 μM for both FFA and NFA in the three vessels. Iberiotoxin, a selective blocker of the BKCa, suppressed the enhancement of the BKCa by FFA and NFA. The KV blocker 4-AP had no effect on the fenamates-induced K+-current enhancement. We conclude that FFA and NFA blocked the vascular gap junction mediated electrical couplings uniformly in arterioles of the three vascular beds, and complete electrical isolation of the recorded VSMC is obtained at ≧300 μM; FFA and NFA also activate BKCa channels in the arteriolar smooth muscle cells in addition to their known inhibitory effects on chloride channels.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalEuropean Journal of Pharmacology
Volume703
Issue number1-3
DOIs
StatePublished - Mar 5 2013

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Keywords

  • Arteriole
  • Electrical coupling
  • Flufenamic acid
  • Gap junction
  • Niflumic acid
  • Potassium channel

ASJC Scopus subject areas

  • Pharmacology

Cite this

Li, X. Z., Ma, K. T., Guan, B. C., Li, L., Zhao, L., Zhang, Z. S., Si, J. Q., & Jiang, Z. G. (2013). Fenamates block gap junction coupling and potentiate BKCa channels in guinea pig arteriolar cells. European Journal of Pharmacology, 703(1-3), 74-82. https://doi.org/10.1016/j.ejphar.2013.02.004