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Feedback Regulation of Calcium Concentration

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In Vivo Calcium Imaging of Lateral-line Hair Cells in Larval Zebrafish
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Zinc increases ciliary beat frequency in a calcium-dependent manner.

Bradford A Woodworth1, Shaoyan Zhang, Edwin Tamashiro

  • 1Otolaryngology, Department of Surgery, University of Alabama-Birmingham, Birmingham, Alabama, USA. bwoodwo@hotmail.com

American Journal of Rhinology & Allergy
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Zinc chloride significantly increases respiratory ciliary beat frequency (CBF) by activating calcium-dependent P2X receptors. This finding suggests zinc is a promising agent for enhancing mucociliary clearance.

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Area of Science:

  • Respiratory physiology
  • Ion channel function
  • Mucociliary clearance

Background:

  • Respiratory ciliary beat frequency (CBF) is dynamically regulated by intracellular calcium (Ca2+) fluxes.
  • P2X receptors (P2XR) are extracellular ATP-gated, Ca2+-permeable cation channels involved in Ca2+ regulation.
  • Zinc is known to increase intracellular Ca2+ via P2XR activation in a sodium (Na+)-free environment.

Purpose of the Study:

  • To investigate the hypothesis that topical zinc increases CBF in a Ca2+-dependent manner through P2XR activation.
  • To explore the role of zinc in modulating respiratory tract mucociliary clearance.

Main Methods:

  • Mouse sinonasal air-liquid interface cultures were utilized.
  • Apical surfaces were exposed to zinc in a Na+-free solution, with or without Ca2+.
  • High-speed digital video imaging (100 frames/s) was used to analyze CBF.

Main Results:

  • Zinc chloride (50 µM) combined with calcium chloride (3 mM) resulted in a fourfold increase in CBF (from 5.99 ± 3.16 Hz to 22.4 ± 4.33 Hz).
  • This stimulatory effect of zinc on CBF was abolished in the presence of extracellular Na+.
  • The observed effect was also found to be pH-dependent.

Conclusions:

  • Zinc stimulates respiratory ciliary beat frequency (CBF) in a calcium-dependent manner, likely via P2X receptor activation.
  • These findings highlight zinc as a potential therapeutic agent for enhancing mucociliary clearance in respiratory conditions.