Pharmacology of Store-operated Calcium Channels

Measuring store-operated calcium entry and Icrac. A) Receptor agonists and Ca²⁺-depleting agents (e.g., thapsigargin) induce a biphasic increase in cytoplasmic Ca²⁺, most clearly revealed by protocols involving discharge of Ca²⁺ stores in the absence of extracellular Ca²⁺ (dotted line) followed by restoration of extracellular Ca²⁺. B) The current underlying store-operated Ca²⁺ entry, I_crac, is generally measured by means of the whole-cell patch-clamp technique, utilizing IP₃ and a calcium chelator in the patch pipet solution to deplete Ca²⁺ stores. C) Depletion of Ca²⁺ stores while measuring whole-cell currents reveals a relatively slowly developing inward current, I_crac. Depending on the recording configuration and cell types, these currents are typically small, in the range of 0.5 – 3.0 pA/pF. D) I_crac shows strong inward rectification in the current–voltage relationship, as is expected for a Ca²⁺-selective channel as intracellular Ca²⁺ concentrations are extremely low.