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Review

Selective permeability of voltage-gated calcium channels

William A. Sather

Advances based on experiment and theory are converging upon a structural description of the selectivity mechanism of voltage-gated calcium channels. The emerging description differs from that for potassium channels, which make use of a stiff filter lined with main chain carbonyl oxygens that snugly fit K⁺ ions. Instead, calcium channels use a selectivity filter composed of the side chain carboxylate oxygen atoms of a cluster of four glutamate residues (EEEE locus). These carboxylate-bearing side chains are thought to project into the aqueous lumen of the pore where they sort Ca²⁺ from other would-be permeant ions. The EEEE locus is evidently flexible: it can tightly bind a single Ca²⁺ ion in order to block Na+ flux but rearranges to accommodate multiple Ca2+ ions in order to allow high Ca²⁺ flux. The four glutamates are not functionally equivalent, an observation that is suspected to be important for Ca²⁺ passage through the selectivity filter. This chapter summarizes the experimental results that support these conclusions and the theoretical models that have been proposed to explain how calcium channels can be at once highly selective and yet readily permeated.

Authors

William A. Sather

University of Colorado Denver