Journal
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
Volume 170, Issue 1, Pages 67-75Publisher
ELSEVIER
DOI: 10.1016/j.resp.2009.12.001
Keywords
P2X receptors; pH; Sodium; Zinc; Cal(2+) entry
Categories
Funding
- Hungarian Health Science Council [ETT 146/2006]
- OTKA [K79189, NF 68563]
- 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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