Irisin relaxes rat trachea via KV channels, KATP channels, and BKCa channels

Abstract

Background: This study aimed to investigate the effects of irisin on rat tracheal smooth muscle contraction-relaxation responses and the roles of voltage-gated potassium (K-V) channels, ATP-sensitive potassium (K-ATP) channels, and large-conductance calcium-activated potassium (BKCa) channels in these effects. Methods: Isometric contraction and relaxation responses of tracheal segments were measured using the tissue bath method. Submaximal contractions were induced by ACh (10(-5) M) or KCl (60 mM), and then concentration-response curves of irisin (10(-9) to 10(-6) M) were obtained. For the temporal control, a double-distilled water group was formed. ACh and irisin were added to the baths after tracheal segments were incubated with 4-AP (K-V channel blocker), glibenclamide (K-ATP channel blocker), TEA, and iberiotoxin (BKCa channel blockers) to assess the role of K+ channels. In addition, a vehicle group was performed for the solvent dimethyl sulfoxide (DMSO). Results: Irisin exhibited the relaxant effects in tracheal segments precontracted with both ACh and KCl at concentrations of 10(-8)-10(-6) M (p<0.05). Besides, incubations of 4-AP, glibenclamide, TEA, and iberiotoxin significantly inhibited the irisin-mediated relaxation (p<0.05), whereas DMSO incubation did not modulate irisin responses (p>0.05). Conclusion: In conclusion, the first physiological results on the relaxant effects of irisin in rat trachea were obtained. Our findings demonstrated that irisin mediates concentration-dependent relaxation in rat tracheas. Moreover, the present study reported for the first time that irisin-induced bronchorelaxation is associated with the activity of the K+ channels.