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

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 tau(f) approximate to 0.2 ms and tau(s) approximate to 10 ms), which can be accounted for by biphasic Ca2+ transients following light photolysis. We estimated the Ca2+-binding rate constant k(b) (approximate to 1.8 x 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 Ca2+ transients in the vicinity of VGCCs during action potentials.