Role of extracellular na%2b, ca2%2b-activated cl - channels and bk channels in the contraction of ca2%2b store-depleted tracheal smooth muscle Article uri icon


  • In the present study, we investigated the series of events involved in the contraction of tracheal smooth muscle induced by the re-addition of Ca 2%2b in an in vitro experimental model in which Ca2%2b stores had been depleted and their refilling had been blocked by thapsigargin. Mean (±SEM) contraction was diminished by: (i) inhibitors of store-operated calcium channels (SOCC), namely 100 μmol/L SKF-96365 and 100 μmol/L 1-(2-trifluoromethylphenyl) imidazole (to 66.3 ± 4.4 and 41.3 ± 5.2%25 of control, respectively); (ii) inhibitors of voltage-gated Ca2%2b channels CaV1.2 channels, namely 1 μmol/L nifedipine and 10 μmol/L verapamil (to 86.2 ± 3.4 and 76.9 ± 5.9%25 of control, respectively); and (iii) 20 μmol/L niflumic acid, a non-selective inhibitor of Ca2%2b-dependent Cl- channels (to 41.1 ± 9.8%25 of control). In contrast, contraction was increased 2.3-fold by 100 nmol/L iberiotoxin, a blocker of the large-conductance Ca2%2b-activated K %2b (BK) channels. Furthermore, contraction was significantly inhibited when Na%2b in the bathing solution was replaced by N-methyl-d-glucamine (NMDG%2b) to 39.9 ± 7.2%25 of control, but not when it was replaced by Li%2b (114.5 ± 24.4%25 of control). In addition, when Na%2b had been replaced by NMDG%2b, contractions were further inhibited by both nifedipine and niflumic acid (to 3.0 ± 1.8 and 24.4 ± 8.1%25 of control, respectively). Nifedipine also reduced contractions when Na%2b had been replaced by Li%2b (to 10.7 ± 3.4%25 to control), the niflumic acid had no effect (116.0 ± 4.5%25 of control). In conclusion, the data of the present study demonstrate the roles of SOCC, BK channels and CaV1.2 channels in the contractions induced by the re-addition of Ca2%2b to the solution bathing guinea-pig tracheal rings under conditions of Ca2%2b-depleted sacroplasmic reticulum and inhibition of sarcoplasmic/endoplasmic reticulum calcium ATPase. The contractions were highly dependent on extracellular Na%2b, suggesting a role for SOCC in mediating the Na%2b influx. © 2009 Blackwell Publishing Asia Pty Ltd.

publication date

  • 2009-01-01