Zn and Cav2.3

Z2+ sensitivity of high- and low-voltage activated calcium channels.

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Z2+ sensitivity of high- and low-voltage activated calcium channels.

Biophys J. 2007 May 25;

Authors: Sun HS, Hui K, Lee DW, Feng ZP

The essential cation zinc (Z(2+)) blocks voltage-dependent calcium channels (VDCCs) in several cell types, which exhibit different sensitivities to Z(2+). The specificity of the Z(2+) effect on VDCC subtypes has not been systematically investigated. In this study, we used a transient protein expression system to determine the Z(2+) effect on low- and high-voltage activated channels. We found that in Ba(2+), the IC50 value of Z(2+) was alpha1 subunit-dependent with lowest for CaV1.2, and highest for CaV3.1; the sensitivity of the channels to Z(2+) was approximately ranked as CaV1.2 > CaV3.2 > CaV2.3 > CaV2.2 = CaV 2.1 >/= CaV3.3 = CaV3.1. Although the CaV2.2 and CaV3.1 channels had similar IC50 for Zn(2+) in Ba(2+), the CaV2.2, but not CaV3.1 channels, had ~10 fold higher IC50 to Zn(2+) in Ca(2+). The reduced sensitivity of CaV2.2 channels to Zn(2+) in Ca(2+) was partially reversed by disrupting a putative EF-hand motif located external to the selectivity filter EEEE locus. Thus, our findings support the notion that the Zn(2+) block, mediated by multiple mechanisms, may depend on conformational changes surrounding the alpha1 pore regions. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of zinc on various Ca(2+) channel subtypes.

PMID: 17526568 [PubMed - as supplied by publisher]