4.2 Article

Calcium entry is regulated by Zn2+ in relation to extracellular ionic environment in human airway epithelial cells

Journal

RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
Volume 170, Issue 1, Pages 67-75

Publisher

ELSEVIER
DOI: 10.1016/j.resp.2009.12.001

Keywords

P2X receptors; pH; Sodium; Zinc; Cal(2+) entry

Funding

  1. Hungarian Health Science Council [ETT 146/2006]
  2. OTKA [K79189, NF 68563]
  3. Hungarian Academy of Sciences

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The extracellular pH, sodium and divalent cation concentrations influence the ATP-induced changes in cytosolic Ca2+ concentration ([Ca2+](i)). This elevation of [Ca2+](i) and activation of Ca2+-dependent Cl- channels represent a possible therapeutic approach in cystic fibrosis (CF). We investigated the changes of [Ca2+](i) in different external ionic environment, and P2X purinergic receptors (P2XRs) expression in the control and CF airway epithelial cells. The parallel removal of Na+ and alkalinization of the extracellular solution increased the amplitude of sustained ATP-induced Ca2+ signals independent of wild-type or mutant CFTR expression. The ATP-induced Ca2+ entry was either inhibited or stimulated by Zn2+ depending on the extracellular Na+ concentration. In Na+-free environment, Zn2+ and other divalent cations elicited a biphasic Ca2+ signal. Immunohistochemical data suggest that, multiple subtypes of P2XRs are expressed in these airway epithelial cells. In conclusion, Ca2+ entry is finely regulated by external ionic environment. Therefore. we speculate that properly compiled aerosols could influence efficacy of zinc-based therapy in CF. (C) 2009 Elsevier B.V. All rights reserved.

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