Extrapolating microdomain Ca(2+) dynamics using BK channels as a Ca(2+) sensor.

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 ?f???0.2 ms and ?s???10?ms), which can be accounted for by biphasic Ca(2+) transients following light photolysis. We estimated the Ca(2+)-binding rate constant kb (?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.

SUBMITTER: Hou P 

PROVIDER: S-EPMC4726033 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature