Extrapolating microdomain Ca2+ dynamics using BK channels as a Ca2+ sensor

Panpan Hou, Feng Xiao, Haowen Liu, Ming Yuchi, Guohui Zhang, Ying Wu, Wei Wang, Wenping Zeng, Mingyue Ding, Jianming Cui, Zhengxing Wu, Lu Yang Wang, Jiuping Ding

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7 Scopus citations


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 τf≈0.2 ms and τs≈10 ms), which can be accounted for by biphasic Ca2+ transients following light photolysis. We estimated the Ca2+-binding rate constant kb (≈1.8×108M-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.

Original languageEnglish
Article number17343
JournalScientific reports
StatePublished - Jan 18 2016


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