Ca2+‐independent activation of BKCa channels at negative potentials in mammalian inner hair cells
Ca2+‐independent activation of BKCa channels at negative potentials in mammalian inner hair cells
复制标题
哺乳动物内毛细胞负电位下 Ca2+ 独立激活 BKCa 通道
DOI：
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
D. Oliver
中科院分区：
文献类型：
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作者：
Henrike Thurm;B. Fakler;D. Oliver
The defining characteristic of large‐conductance Ca2+‐ and voltage‐activated K+ channels (BKCa) is their allosteric activation by two distinct stimuli, membrane depolarization and cytosolic Ca2+ ions. In this allosteric gating, increasing cytosolic Ca2+ concentration ([Ca2+]i) shifts the depolarization required for channel opening into the physiological voltage range. In fact, according to present knowledge, elevation of [Ca2+]i to micromolar levels is the only means to activate BKCa at membrane potentials below 0 mV. We recorded BKCa‐mediated currents from auditory inner hair cells (IHCs) in acutely isolated organs of Corti using the patch‐clamp technique in whole‐cell and excised patch configuration. In inside‐out and outside‐out patches, activation of BKCa channels from IHCs showed the prototypic sensitivity to increased [Ca2+]i. However, channel activation at 0 [Ca2+]i occurred at unusually negative potentials (half‐maximal activation (Vh) around 0 mV), indicating that a large fraction of the channels can be activated at physiological voltages without elevated [Ca2+]i. In intact IHCs, the activation curve of BKCa currents recorded in whole‐cell configuration exhibited a Vh of −42 mV together with a high voltage dependence (slope factor of 10 mV) and submillisecond onset of current. Surprisingly, this activation was independent of changes in local [Ca2+]i as shown by experiments that interfered with Ca2+ influx through voltage‐gated Ca2+ (Cav) channels, release of Ca2+ from internal stores, or intracellular buffer capacity. This behaviour is not due to β‐subunits of BKCa (BKβ), as genetic inactivation of the β‐subunit expressed in IHCs, KCNMB1, did not affect BKCa gating. We conclude that the BKCa channel protein in IHCs may be modified in order to rapidly activate and deactivate at resting [Ca2+]i. Our results suggest that BKCa may function as a purely voltage‐gated K+ channel with exceptionally rapid activation kinetics, challenging the view that both increased cytosolic Ca2+ and depolarization are generally required for activation of BKCa.
DOI：
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发表时间：
1986-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
G. Meissner
通讯作者：
G. Meissner
DOI：
10.1073/pnas.96.7.4137
发表时间：
1999-03-30
影响因子：
11.1
作者：
Wallner, M;Meera, P;Toro, L
通讯作者：
Toro, L
影响因子：
2.5
作者：
Skinner, LJ;Enée, V;Dulon, D
通讯作者：
Dulon, D