Induced by the depletion of ER calcium store, the calcium influx through calcium release-activated calcium (CRAC) channels is an ubiquitous way of Ca
influx for most cell types. This process is mediated by STIM protein, ER calcium sensor, and PM localized Orai calcium channels. Biophysical characterization of this STIM-Orai-mediated current, or I
, with whole-cell patch-clamp technique is essential for revealing the molecular mechanisms underlying the process of STIM-Orai activation or modulation. Here we describe one commonly used procedure of monitoring CRAC activity with whole-cell patch-clamp technique.