Effects of zinc ions on the membrane currents in the isolated endothelial cells of guinea-pig mesenteric artery

Abstract

Some of heavy-metal ions are known to increase [Ca²⁺]_i in many kinds of cells including vascular endothelial cells. To investigate the effects of Zn²⁺, a sheet of endothelial cells was isolated from a guinea-pig mesentericartery and conventional whole-cell clamp experiments were performed. Zn²⁺ (<=20 μM) decreased the resting membrane conductance which was thought to be due to nonselective cation channels. Inward rectifier K⁺ channels also contributed to the resting conductance, however, these channels were not blocked by Zn²⁺. These concentrations of Zn²⁺ seemed also to inhibit Ca²⁺ influx, because the membrane currents induced by repeated applications of agonist such as ACh decreased. Zn²⁺ at higher concentrations additionally activated Ca²⁺-activated K⁺ and Cl⁻ channels indicating that Zn²⁺ indeed increased [Ca²⁺]_i in our preparations. As Zn²⁺ could induce these currents in the absence of the external Ca²⁺, Zn²⁺ likely released Ca²⁺ from the intracellular store sites. Both ACh-induced and ATP-induced currents were suppressed in the presence of 50 μM-Zn²⁺, and Zn²⁺ seems to bind and modify the receptor proteins for such agonists to increase [Ca²⁺]_i. Although the concentrations of Zn²⁺ used in the present experiments were beyond the physiological range, Zn²⁺ may be a good tool to investigate the intracellular Ca²⁺handling in the vascular endothelial cells. [J Physiol Sci. 2008;58 Suppl:S69]