In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-01-18)
Abstract:
Ca 2+ ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca 2+ dynamics local to the Ca 2+ source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca 2+ 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 Ca 2+ channels (VGCCs), spatially enabling the coupling of the intracellular Ca 2+ 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 Ca 2+ local transients in the microdomain of VGCCs. Accordingly, we applied flash photolysis of caged Ca 2+ to activate BK channels and determine their intrinsic sensitivity to Ca 2+ . We found that uncaging Ca 2+ 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 Ca 2+ transients following light photolysis. We estimated the Ca 2+ -binding rate constant k b (≈1.8 × 10 8 M −1 s −1 ) for mSlo1 and further developed a model in which BK channels act as a calcium sensor capable of quantitatively predicting local microdomain Ca 2+ transients in the vicinity of VGCCs during action potentials.
Type of Medium:
Online Resource
ISSN:
2045-2322
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2016
detail.hit.zdb_id:
2615211-3
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