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Return of the Electric Binding Site

The Journal of General Physiology
The Rockefeller University Press
Publication Date
DOI: 10.1085/jgp.200810135
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untitled Th e Jo ur na l o f G en er al P hy si o lo g y The Rockefeller University Press $30.00 J. Gen. Physiol. Vol. 132 No. 5 487–489 487 C O M M E N TA RY The BK-type Ca 2+ -activated K + channel has been the sub- ject of increasingly detailed mechanistic study since the fi rst recordings of this channel were obtained more than 25 years ago ( Pallotta et al., 1981 ; Latorre et al., 1982 ; Magleby, 2003 ; and references therein). But if you thought that our understanding of the gating of the BK channel and its allosteric regulation by Ca 2+ and trans- membrane voltage had reached its summit, then once again you would be wrong. In a remarkable display of patch-clamping and kinetic analysis appearing in this issue, the bear is poked once again, with this iteration of analysis constrained by high-resolution Ca 2+ dose-re- sponse curves, containing data at 22 (!) different [Ca 2+ ]. Here, Sweet and Cox (see p. 491 ) analyze the two high- affi nity Ca 2+ binding sites of the BK channel using muta- tions to selectively disable each site, and obtain defi nitive results on how the sites behave in isolation and how they might interact with one another in the intact BK channel. A surprising fi nding is that binding to one of the two binding sites is modulated by transmembrane voltage. This intriguing twist opens possibilities for iden- tifying a structural basis for interactions between the voltage sensor and one of the principal Ca 2+ activation sites of the channel. Mysteries of Ca 2+ Activation Despite the functional simplicity of the BK channel, which is activated principally (for the purpose of this Commentary) by cytoplasmic Ca 2+ and depolarization, and our high level of understanding of the mechanisms underlying its activation, there are still many intricacies of this channel that are not well understood. And these details are not trivial; because BK channels serve as cyto- plasmic Ca

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