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Calcium activation of BKCa potassium channels lacking the calcium bowl and RCK domains

Nature volume 420, pages 499–502 (2002)Cite this article

Abstract

In many physiological systems such as neurotransmitter release, smooth muscle relaxation and frequency tuning of auditory hair cells, large-conductance calcium-activated potassium (BKCa) channels create a connection between calcium signalling pathways and membrane excitability1,2,3,4. BKCa channels are activated by voltage and by micromolar concentrations of intracellular calcium. Although it is possible to open BKCa channels in the absence of calcium5,6,7,8,9, calcium binding is essential for their activation under physiological conditions. In the presence of intracellular calcium, BKCa channels open at more negative membrane potentials5,10,11,12,13,14. Many experiments investigating the molecular mechanism of calcium activation of the BKCa channel have focused on the large intracellular carboxy terminus, and much evidence supports the hypothesis that calcium-binding sites are located in this region of the channel. Here we show that BKCa channels that lack the whole intracellular C terminus retain wild-type calcium sensitivity. These results show that the intracellular C terminus, including the ‘calcium bowl’ and the RCK domain, is not necessary for the calcium-activated opening of these channels.

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Figure 1: The truncated BKCa channel retains normal function.
Figure 2: The truncated BKCa channel is activated by micromolar levels of Ca2+.
Figure 3: Mean open time is altered in truncated BKCa channels.
Figure 4: Data are not contaminated by endogenous BKCa channel subunits.

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Acknowledgements

We thank S. Wiler for help with mutagenesis; and R. Lewis, M. Maduke, J. Trimmer, T. Middendorf, J. Sack and S. Pyott for critically reading the manuscript. R.P. was supported by a training grant from the National Institutes of Health. R.W.A is an investigator for the Howard Hughes Medical Institute.

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  1. Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, 94305-5345, USA

    Rebecca Piskorowski & Richard W. Aldrich

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  1. Rebecca Piskorowski
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  2. Richard W. Aldrich
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Correspondence to Richard W. Aldrich.

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Piskorowski, R., Aldrich, R. Calcium activation of BKCa potassium channels lacking the calcium bowl and RCK domains. Nature 420, 499–502 (2002). https://doi.org/10.1038/nature01199

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