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. 2002 Nov;83(5):2528–2538. doi: 10.1016/S0006-3495(02)75264-8

Localization of divalent cation-binding site in the pore of a small conductance Ca(2+)-activated K(+) channel and its role in determining current-voltage relationship.

Heun Soh 1, Chul-Seung Park 1
PMCID: PMC1302339  PMID: 12414687

Abstract

In our previous study, we proposed that the inwardly rectifying current-voltage (I-V) relationship of small-conductance Ca(2+)-activated K(+) channels (SK(Ca) channels) is the result of voltage-dependent blockade of K(+) currents by intracellular divalent cations. We expressed a cloned SK(Ca) channel, rSK2, in Xenopus oocytes and further characterized the nature of the divalent cation-binding site by electrophysiological means. Using site-directed substitution of hydrophilic residues in K(+)-conducting pathway and subsequent functional analysis of mutations, we identified an amino acid residue, Ser-359, in the pore-forming region of rSK2 critical for the strong rectification of the I-V relationship. This residue interacts directly with intracellular divalent cations and determines the ionic selectivity. Therefore, we confirmed our proposition by localizing the divalent cation-binding site within the conduction pathway of the SK(Ca) channel. Because the Ser residue unique for the subfamily of SK(Ca) channels is likely to locate closely to the selectivity filter of the channels, it may also contribute to other permeation characteristics of SK(Ca) channels.

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Selected References

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