期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：46
页码：18991-18996
DOI：10.1073/pnas.1216953109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming subunit of BK is associated with one of four alternative {beta} subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, {beta}1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca2+ sensitivity. To determine the extent to which {beta} subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK subunit alone and with the different {beta} subunits expressed in Xenopus oocytes ({beta}1, {beta}2IR, {beta}3b, and {beta}4). We found that {beta}1, {beta}2, and {beta}4 stabilize the BK voltage sensor in the active conformation. {beta}3 has no effect on voltage sensor equilibrium. In addition, {beta}4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in {beta}4 channels explains most of their biophysical properties. For channels composed of the subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K+ current activation. In the presence of {beta}1, {beta}2, and {beta}4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps.
