Zinc increases ciliary beat frequency in a calcium-dependent manner

Background: Dynamic regulation of respiratory ciliary beat frequency (CBF) is regulated by fluxes in intracellular calcium (Ca(2+)). P2X receptors (P2XR) are extracellular ATP-gated, Ca(2+)-permeable, nonselective cation channels. Zinc increases intracellular Ca(2+) in a sodium (Na(+))-free environment through activation of P2XR channels. We hypothesize that topical zinc increases CBF in a Ca(2+)-dependent fashion as a result of this mechanism. Methods: The apical surface of mouse sinonasal air-liquid interface cultures were bathed in zinc in a Na(+)-free solution with or without Ca(2+). High-speed digital video imaging captured and analyzed CBF at a sampling rate of 100 frames/s. Results: CBF significantly increased fourfold over baseline from 5.99 +/- 3.16 Hz to 22.4 +/- 4.33 Hz in the presence of zinc chloride (50 micromoles) and calcium chloride (3 mM). This effect is abolished in the presence of extracellular Na(+) and was pH dependent. Conclusion: Zinc stimulates CBF in the presence of Ca(2+) likely through activation of P2X receptors. Thus, zinc represents a promising agent for stimulation of mucociliary clearance. (Am J Rhinol Allergy 24, 6-10, 2010; doi: 10.2500/ajra.2010.24.3379)