Functional coupling between the Na%2b/Ca2%2b exchanger and nonselective cation channels during histamine stimulation in guinea pig tracheal smooth muscle Article uri icon


  • Airway smooth muscle (ASM) contracts partly due to an increase in cytosolic Ca2%2b. In this work, we found that the contraction caused by histamine depends on external Na%2b, possibly involving nonselective cationic channels (NSCC) and the Na%2b/Ca2%2b exchanger (NCX). We performed various protocols using isometric force measurement of guinea pig tracheal rings stimulated by histamine. We observed that force reached 53 ± 1%25 of control during external Na%2b substitution by N-methyl-D-glucamine%2b, whereas substitution by Li%2b led to no significant change (91 ± 1%25). Preincubation with KB-R7943 decreased the maximal force developed (52.3 ± 5.6%25), whereas preincubation with nifedipine did not (89.7 ± 1.8%25). Also, application of the nonspecific NCX blocker KB-R7943 and nifedipine on histamine-precontracted tracheal rings reduced force to 1 ± 3%25, significantly different from nifedipine alone (49 ± 6%25). Moreover, nonspecific NSCC inhibitors SKF-96365 and 2-aminoethyldiphenyl borate reduced force to 1 ± 1%25 and 19 ± 7%25, respectively. Intracellular Ca2%2b measurements in isolated ASM cells showed that KB-R7943 and SKF-96365 reduced the peak and sustained response to histamine (0.20 ± 0.1 and 0.19 ± 0.09 for KB-R, 0.43 ± 0.16 and 0.47 ± 0.18 for SKF, expressed as mean of differences). Moreover, Na%2b-free solution only inhibited the sustained response (0.54 ± 0.25). These data support an important role for NSCC and NCX during histamine stimulation. We speculate that histamine induces Na%2b influx through NSCC that promotes the Ca2%2b entry mode of NCX and Ca V1.2 channel activation, thereby causing contraction. Copyright © 2007 the American Physiological Society.

publication date

  • 2007-01-01