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

abstract

  • Airway smooth muscle (ASM) contracts partly due to an increase in cytosolic Ca2 . In this work, we found that the contraction caused by histamine depends on external Na , possibly involving nonselective cationic channels (NSCC) and the Na /Ca2 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 substitution by N-methyl-D-glucamine , whereas substitution by Li 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 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 -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 influx through NSCC that promotes the Ca2 entry mode of NCX and Ca V1.2 channel activation, thereby causing contraction. Copyright © 2007 the American Physiological Society.
  • 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