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

Respir Physiol Neurobiol. 2010 Jan 31;170(1):67-75. doi: 10.1016/j.resp.2009.12.001. Epub 2009 Dec 6.

Abstract

The extracellular pH, sodium and divalent cation concentrations influence the ATP-induced changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)). This elevation of [Ca(2+)](i) and activation of Ca(2+)-dependent Cl(-) channels represent a possible therapeutic approach in cystic fibrosis (CF). We investigated the changes of [Ca(2+)](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 Ca(2+) signals independent of wild-type or mutant CFTR expression. The ATP-induced Ca(2+) entry was either inhibited or stimulated by Zn(2+) depending on the extracellular Na(+) concentration. In Na(+)-free environment, Zn(2+) and other divalent cations elicited a biphasic Ca(2+) signal. Immunohistochemical data suggest that, multiple subtypes of P2XRs are expressed in these airway epithelial cells. In conclusion, Ca(2+) entry is finely regulated by external ionic environment. Therefore, we speculate that properly compiled aerosols could influence efficacy of zinc-based therapy in CF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Apyrase / pharmacology
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Cell Line, Transformed
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Estrenes / pharmacology
  • Extracellular Fluid / drug effects*
  • Extracellular Fluid / metabolism
  • Gene Deletion
  • Gene Expression Regulation / drug effects
  • Hexokinase / pharmacology
  • Humans
  • Lactones / pharmacology
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyrrolidinones / pharmacology
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X
  • Sesquiterpenes / pharmacology
  • Sodium / metabolism
  • Suramin / pharmacology
  • Transfection / methods
  • Zinc / metabolism
  • Zinc / pharmacology*

Substances

  • Estrenes
  • Lactones
  • Platelet Aggregation Inhibitors
  • Pyrrolidinones
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Sesquiterpenes
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Suramin
  • thapsigargicin
  • Adenosine Triphosphate
  • Sodium
  • Hexokinase
  • Apyrase
  • Zinc
  • Calcium