Change Of TRPV4-SK_ca Complex And Its Effect On Contractile Function In Aged Rat Main Airway Smooth Muscle

ObjectiveTRPV4 is one of the important members of transient receptor potential vanilloid (TRPV) in transient receptor potential (TRP) family. In lots of tissue cells, TRPV4 has important function. In the present study, through the tension measurement of isolated tracheas and Western blot, we investigated change of the interaction of TRPV4 and small-conductance calcium-activated potassium channels (SK3), and the effect of this change on the contraction of the airway smooth muscle in aged rats.Methods1. Animals:The rats included youth group and aged group.2. Tension measurement of isolated tracheas:2.1 Using high potassium solution (60 mM K+) to contract the tracheal rings of the youth and aged rats separately to compare the difference of contractive effect between groups.2.2 Using carbachol to contract the tracheal rings of the youth and aged rats separately to compare the difference of contractive effect between groups.2.3 To observe the effect of TRPV4 channel agonist GSK on carbachol-induced contraction.2.4 The tracheal rings were pretreated by TRPV4 channel inhibitor HC06047 and RN1734 for 20 min. Then we observed the effect of TRPV4 channel agonist GSK on carbachol-induced contraction.3. Western blot:To detect the change of the expression levels of TRPV4 and SK3 in the airway smooth muscle of the youth and aged rats.Results1. There was no significant difference in the contractive effect of high potassium solution on the airway smooth muscle between the youth and aged rats. But carbachol-induced contraction was significantly increased in aged rats compared with that in the youth rats.2. Compared with youth rats, the relaxation effect induced by GSK, an agonist of TRPV4, on carbachol-induced contraction was notably reduced in the aged rats. On the other hand, after the two groups of tracheal rings were pretreated by TRPV4 inhibitor HC06047 and RN1734 separately, the relaxation effect induced by GSK on the contractive effect of carbachol was abolished.3. Western blot result indicated that compared with youth rats, the expression level of TRPV4 was remarkably increased while the expression level of SK3 was apparently decreased in the airway smooth muscle of the aged rats.ConclusionThe increased expression of TRPV4 may be a compensation for the remarkably decreased expression of SK3 in the airway smooth muscle of aged rats. Meanwhile, the change of the expression level of TRPV4-SK3 complex may be closely correlated with the decreased relaxation effect on the smooth muscle of aged rats.