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Functional coupling between the NCX and NSCC during histamine stimulation in guinea‐pig tracheal smooth muscle
Author(s) -
EspinosaTanguma Ricardo,
Algara Paola,
Chrones Tom,
Romero Catalina,
Meza Ulises,
SánchezArmass Sergio,
Sims Stephen M
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a960-c
Airway smooth muscle contractility is due to changes in cytosolic Ca 2+ and depends on external Na + . We propose that the Na + ‐Ca 2+ exchanger (NCX) mediates Ca 2+ influx secondary to intracellular Na + increase through non‐selective cationic channels (NSCC). By performing isometric force measurement of guinea‐pig tracheal rings stimulated by histamine we observed that Na + substitution by N ‐Methyl‐D‐glucamine (NMDG) produced a 47 ± 7% inhibition of peak force, whereas substitution by LiCl led to no significant inhibition (9 ± 2 %). Application of NCX blocker KB‐R7943 relaxed the muscle 98.96 ± 2.8 % whereas vehicle caused no relaxation (2 ± 1.3 %). Also, NSCC blockers SKF‐96365 and 2‐Aminoethyl diphenylborinate (2APB) caused relaxation (91 ±1% for the former and 81 ± 7% for the latter). By measuring intracellular Ca 2+ changes in isolated smooth muscle cells we observed that KB‐R7943 significantly decreased the fluorescence ratio in a second stimulation with histamine (0.70 ± 0.12 for control v.s. 0.49 ± 0.17 for KBR) and that SKF‐96365 also decreased the fluorescence ratio (0.75 ± 0.25 for control v.s. 0.27 ± 0.10 for SKF). Altogether, these data strongly suggest an important role for the NSCC in generating a cationic current that sets the NCX in a Ca 2+ entry mode and that this in turn is crucial to sustain the histamine‐induced contraction. Support by CONACyT ‐165845, C05‐FAI‐10‐3.21, C06‐FAI‐03‐4.7, PIFI 3.1 and CIHR.