文章基本信息

标题：Extrapolating microdomain Ca²⁺ dynamics using BK channels as a Ca²⁺ sensor
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作者：Panpan Hou ; Feng Xiao ; Haowen Liu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2016
卷号：6
DOI：10.1038/srep17343
出版社：Springer Nature
摘要：Ca²⁺ ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca²⁺ dynamics local to the Ca²⁺ source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca²⁺ stores, is difficult to delineate. Large-conductance calcium-activated K⁺ (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca²⁺ channels (VGCCs), spatially enabling the coupling of the intracellular Ca²⁺ signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca²⁺ local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca²⁺ to activate BK channels and determine their intrinsic sensitivity to Ca²⁺. We found that uncaging Ca²⁺ activated biphasic BK currents with fast and slow components (time constants being τ_f ≈ 0.2 ms and τ_s ≈ 10 ms), which can be accounted for by biphasic Ca²⁺ transients following light photolysis. We estimated the Ca²⁺-binding rate constant k_b (≈1.8 × 10⁸ M⁻¹s⁻¹) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca²⁺ transients in the vicinity of VGCCs during action potentials.