Store-refilling involves both L-type Ca²⁺ channels and reverse-mode Na⁺/Ca²⁺ exchange

¹ Firestone Institute for Respiratory Health, St. Joseph's Healthcare and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5

^* To whom correspondence should be addressed. E-mail: janssenl{at}mcmaster.ca.

	Abstract

In this study we examined the relative contribution of two voltage-regulated Ca²⁺ influx pathways in store-refilling:1)L-type-Ca²⁺ channels; 2)the reverse-mode of the Na+/Ca²⁺-exchanger(NCX).

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

Pretreating tissues with cromakalim significantly reduced successive contractions. Zero-Ca²⁺ bathing media abolished contractions, an effect that was completely reversed upon reintroduction of Ca²⁺. Inhibition of L-type-Ca²⁺ channels, with nifedipine, significantly reduced contractions. Similarly, inhibition of the reverse-mode of the NCX, with KB-R7943, significantly reduced contractions. However, neither nifedipine nor KB-R7943 alone reduced contractions to the same levels as was observed under zero-Ca²⁺ conditions. However, concurrent treatment with nifedipine and KB-R7943 nearly 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 blot revealed the presence of three bands at 160, 120 and 110kDa. The 120 and 110kDa bands were identified as variably-spliced NCX isoforms NCX1.1 and NCX1.3, respectively.

Altogether our data suggest that influx of Ca²⁺ through both L-type-Ca²⁺ channels and reverse-mode-NCX is necessary for complete store-refilling in airway smooth muscle.

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