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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/L191    most recent 00485.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Algara-Suárez, P. Articles by Espinosa-Tanguma, R. Search for Related Content PubMed PubMed Citation Articles by Algara-Suárez, P. Articles by Espinosa-Tanguma, R.

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

¹Departmento de Fisiología, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México, and ²Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada

Submitted 20 December 2006 ; accepted in final form 16 April 2007

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% of control during external Na⁺ substitution by N-methyl-D-glucamine⁺, whereas substitution by Li⁺ led to no significant change (91 ± 1%). Preincubation with KB-R7943 decreased the maximal force developed (52.3 ± 5.6%), whereas preincubation with nifedipine did not (89.7 ± 1.8%). Also, application of the nonspecific NCX blocker KB-R7943 and nifedipine on histamine-precontracted tracheal rings reduced force to 1 ± 3%, significantly different from nifedipine alone (49 ± 6%). Moreover, nonspecific NSCC inhibitors SKF-96365 and 2-aminoethyldiphenyl borate reduced force to 1 ± 1% and 19 ± 7%, 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.

airway smooth muscle; KB-R7943; SKF-96365

This article has been cited by other articles:

				A. Pezier, Y. V. Bobkov, and B. W. Ache The Na+/Ca2+ Exchanger Inhibitor, KB-R7943, Blocks a Nonselective Cation Channel Implicated in Chemosensory Transduction J Neurophysiol, March 1, 2009; 101(3): 1151 - 1159. [Abstract] [Full Text] [PDF]