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Store-refilling involves both L-type calcium channels and reverse-mode sodium–calcium exchange in airway smooth muscle

Firestone Institute for Respiratory Health, St. Joseph’s Healthcare and Dept of Medicine, McMaster University, Hamilton, ON, Canada.

CORRESPONDENCE: L. J. Janssen, L-314, St. Joseph’s Healthcare, 50 Charlton Ave. East, Hamilton, ON, Canada L8N 4A6. Fax: 1 9055406510. E-mail: janssenl{at}mcmaster.ca

Keywords: Airway smooth muscle, calcium-handling, L-type calcium channel, membrane depolarisation, reverse-mode sodium–calcium exchanger, sarcoplasmic reticulum

Received: January 22, 2007
Accepted March 29, 2007

The aim of the present study was to examine the relative contributions to store-refilling of the two following voltage-regulated calcium ion influx pathways: 1) L-type-Ca²⁺ channels; and 2) the reverse-mode of the sodium–calcium exchanger (NCX).

Successive acetylcholine-induced contractions, triggered in bovine tracheal smooth muscle strips, were measured to determine the effect of intervention on contractions as an indication of the extent of store-refilling.

Pre-treating the tissues with cromakalim significantly reduced the magnitude of successive contractions. Zero-Ca²⁺ bathing media abolished the contractions, an effect that was completely reversed upon reintroduction of Ca²⁺. Inhibition of L-type Ca²⁺ channels, with nifedipine, significantly reduced the magnitude of the contractions. Similarly, inhibition of the reverse-mode of the NCX, with KB-R7943, significantly reduced the magnitude of the contractions. However, neither nifedipine nor KB-R7943 alone reduced contractions to the same extent as observed under zero-Ca²⁺ conditions. Concurrent treatment with nifedipine and KB-R7943 almost abolished successive contractions. Furthermore, concurrent treatment with nifedipine and zero-Na⁺ bathing media displayed a significantly greater effect than nifedipine alone. Probing the expression of NCX1 isoforms by Western blotting revealed the presence of three bands of 160, 120 and 110 kDa. The 120- and 110-kDa bands were identified as variably spliced NCX isoforms, NCX1.1 and NCX1.3, respectively.

Taken together, these data suggest that influx of calcium ions through both L-type calcium channels and the reverse-mode of the sodium–calcium exchanger is necessary for complete store-refilling in airway smooth muscle.

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				S. A. Hirota and L. J. Janssen Sodium and asthma: something borrowed, something new? Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1369 - L1373. [Abstract] [Full Text] [PDF]