Bestrophins are a newly discovered family of Cl− channels, some members of which are activated by intracellular Ca2+. So far, all studies were carried out with whole-cell recordings from plasmid-transfected cultured cells, so it is unclear whether Ca2+ activates bestrophin through a metabolic mechanism or in a more direct way. We report here experiments that addressed this question with excised, inside-out membrane patches. We chose human bestrophin-4 (hBest4) for heterologous expression because it gave particularly large Cl− currents when expressed, thus allowing detection even in excised membrane patches. hBest4 gave a negligible Cl− current in a Ca2+-free solution on the cytoplasmic (bath) side, but produced a Cl− current that was activated by Ca2+ in a dose-dependent manner, with a K1/2 of 230 nM. Thus, Ca2+ appears to activate the bestrophin Cl− channel without going through a freely diffusible messenger or through protein phosphorylation. Because the activation and deactivation kinetics were very slow, however, we cannot exclude the involvement of a membrane-associated messenger.
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1 June 2006
Communication|
May 15 2006
Ca2+-activated Cl− Current from Human Bestrophin-4 in Excised Membrane Patches
Takashi Tsunenari,
Takashi Tsunenari
1Department of Neuroscience
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Jeremy Nathans,
Jeremy Nathans
1Department of Neuroscience
2Department of Ophthalmology
3Department of Molecular Biology and Genetics,
4Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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King-Wai Yau
King-Wai Yau
1Department of Neuroscience
2Department of Ophthalmology
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Takashi Tsunenari
1Department of Neuroscience
Jeremy Nathans
1Department of Neuroscience
2Department of Ophthalmology
3Department of Molecular Biology and Genetics,
4Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205
King-Wai Yau
1Department of Neuroscience
2Department of Ophthalmology
Correspondence to T. Tsunenari: [email protected]
Abbreviations used in this paper: hBest, human bestrophin; mBest, mouse bestrophin; xBest, Xenopus bestrophin; RPE, retinal pigment epithelial.
Received:
February 27 2006
Accepted:
April 25 2006
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2006
J Gen Physiol (2006) 127 (6): 749–754.
Article history
Received:
February 27 2006
Accepted:
April 25 2006
Citation
Takashi Tsunenari, Jeremy Nathans, King-Wai Yau; Ca2+-activated Cl− Current from Human Bestrophin-4 in Excised Membrane Patches . J Gen Physiol 1 June 2006; 127 (6): 749–754. doi: https://doi.org/10.1085/jgp.200609527
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