Measuring the influence of the BKCa {beta}1 subunit on Ca2+ binding to the BKCa channel.

The Journal of General Physiology
Tara-Beth Sweet, Daniel H Cox

Abstract

The large-conductance Ca(2+)-activated potassium (BK(Ca)) channel of smooth muscle is unusually sensitive to Ca(2+) as compared with the BK(Ca) channels of brain and skeletal muscle. This is due to the tissue-specific expression of the BK(Ca) auxiliary subunit beta1, whose presence dramatically increases both the potency and efficacy of Ca(2+) in promoting channel opening. beta1 contains no Ca(2+) binding sites of its own, and thus the mechanism by which it increases the BK(Ca) channel's Ca(2+) sensitivity has been of some interest. Previously, we demonstrated that beta1 stabilizes voltage sensor activation, such that activation occurs at more negative voltages with beta1 present. This decreases the work that Ca(2+) must do to open the channel and thereby increases the channel's apparent Ca(2+) affinity without altering the real affinities of the channel's Ca(2+) binding sites. To explain the full effect of beta1 on the channel's Ca(2+) sensitivity, however, we also proposed that there must be effects of beta1 on Ca(2+) binding. Here, to test this hypothesis, we have used high-resolution Ca(2+) dose-response curves together with binding site-specific mutations to measure the effects of beta1 on Ca(2+) binding. We find that coex...Continue Reading

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Citations

Nov 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gustavo F ContrerasRamon Latorre
Sep 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Gonzalo BudelliLawrence Salkoff
Dec 29, 2009·The Journal of Biological Chemistry·Shangwei HouToshinori Hoshi
Nov 17, 2010·The Journal of General Physiology·Antonios PantazisRiccardo Olcese
Dec 14, 2011·The Journal of General Physiology·Aleksandra GruslovaBin Wang
Jan 3, 2013·Clinical and Experimental Pharmacology & Physiology·Paulo A SaldanhaIgnacio Verde
Mar 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Toshinori HoshiShangwei Hou
Jan 1, 2014·Pflügers Archiv : European journal of physiology·Pedro MartínVerónica Milesi
Apr 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Karen CastilloRamon Latorre
Jan 31, 2014·Channels·Trey S RottgenGregory M Dick
Nov 2, 2016·The Journal of General Physiology·Guruprasad Kuntamallappanavar, Alex M Dopico
May 3, 2013·Physiology·T HoshiR Olcese
Oct 21, 2010·Physiological Reviews·Henrike BerkefeldUwe Schulte
Jun 8, 2019·The Journal of Physiology·Enrique BalderasRiccardo Olcese
Nov 4, 2016·Physiological Reviews·Ramon LatorreOsvaldo Alvarez
Aug 15, 2018·Frontiers in Molecular Neuroscience·Aravind S KshatriTeresa Giraldez
Jan 8, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Fiona M LynchAnthony M Heagerty
Oct 1, 2017·Experimental and Therapeutic Medicine·Yuan-Yuan HanJun-Qiang Si
Jul 27, 2012·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·M FranceH Xu
May 7, 2021·Channels·Ana L González-CotaEnrique Balderas

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Methods Mentioned

BETA
transfection

Software Mentioned

Igor Pro
HEKA
MaxChelator

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