The 1.3 isoform of Na+-Ca 2+ exchanger expressed in guinea pig tracheal smooth muscle is less sensitive to KB-R7943.

Department of Physiology, Facultad de Medicina de la Universidad Autónoma de San Luis Potosí, Av. V. Carranza 2405, San Luis Potosí, San Luis Potosí 78210, Mexico.
Journal of physiology and biochemistry (Impact Factor: 2.5). 06/2010; 66(2):117-25. DOI: 10.1007/s13105-010-0016-8
Source: PubMed

ABSTRACT The sodium-calcium exchanger (NCX) plays a major role in the regulation of cytosolic Ca(2+) in muscle cells. In this work, we performed force experiments to explore the role of NCX during contraction and relaxation of Cch-stimulated guinea pig tracheal smooth muscle strips. This tissue showed low sensitivity to NCX inhibitor KB-R7943 (IC50, 57 +/- 2 microM), although a complete relaxation was obtained by NCX inhibition at 100 microM. Interestingly, relaxation after washing the agonist was prolonged in the absence of external Na(+), whereas washing without Na(+) and in the presence of KB-R7943 resembled control conditions with physiological solution. Altogether, this suggests the reversal of NCX to a Ca(2+) influx mode by the manipulation on the Na(+) gradient, which can be inhibited by KB-R7943. In order to understand the low sensitivity to KB-R7943, we studied the molecular aspects of the NCX expressed in this tissue and found that the isoform of NCX expressed is 1.3, similar to that described in human tracheal smooth muscle. Sequencing revealed that amino acid 19 in exon B is phenylalanine, whereas in its human counterpart is leucine, and that the first amino acid after exon D is aspartate instead of glutamate in humans. Results herein presented are discussed in term of their possible functional implications in the exchanger activity and thus in airway physiology.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features including 1) [Ca(2+)]i, contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, 4) release of pro- vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types such as epithelium, fibroblasts and nerves. These diverse effects of ASM "activity" result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening and fibrosis that influences compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard, and helps set the stage for future research towards understanding the pathways regulating ASM, and in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, COPD and pulmonary fibrosis.
    AJP Lung Cellular and Molecular Physiology 10/2013; · 3.52 Impact Factor


Available from
Jan 7, 2015