D. Salvail et al., DIRECT MODULATION OF TRACHEAL CL--CHANNEL ACTIVITY BY 5,6-EET AND 11,12-EET, American journal of physiology. Lung cellular and molecular physiology, 19(3), 1998, pp. 432-441
Using microelectrode potential measurements, we tested the involvement
of Cl- conductances in the hyperpolarization induced by 5,6- and 11,1
2- epoxyeicosatrienoic acid (EET) in airway smooth muscle (ASM) cells.
5,6-EET and 11,18-EET (0.75 mu M) caused -5.4 +/- 1.1- and -3.34 +/-
0.95-mV hyperpolarizations, respectively, of rabbit tracheal cells (fi
om a resting membrane potential of -53.25 +/- 0.44 mV), with signific
ant residual repolarizations remaining after the Ca2+-activated K+ cha
nnels had been blocked by 10 nM iberiotoxin. In bilayer reconstitution
experiments, we demonstrated that the EETs directly inhibit a Ca2+-in
sensitive Cl- channel from bovine ASM; 1 mu M 5,6-EET and 1.5 mu M 11,
18-EET lowered the unitary current amplitude by 40 (n = 6 experiments)
and 44.7% (n = 4 experiments), respectively. Concentration-dependent
decreases in channel open probability were observed, with estimated IC
50 values of 0.26 mu M for 5,6- and 1.15 mu M for 11,18-EET. Furthermo
re, pharmacomechanical tension measurements showed that both regioisom
ers induced significant bronchorelaxations in epithelium-denuded ASM s
trips. These results suggest that 5,6- and 11,18-EET can act in ASM as
epithelium-derived hyperpolarizing factors.