Store-Operated Ca²⁺ Entry (SOCE) Pathways

Dora Bodnar, Woo Young Chung, Dongki Yang, Jeong Hee Hong, Archana Jha, Shmuel Muallem

Ca(2+) influx by plasma membrane Ca(2+) channels is the crucial component of the receptor-evoked Ca(2+) signal. The two main Ca(2+) influx channels of non-excitable cells are the Orai and TRPC families of Ca(2+) channels. These channels are activated in response to cell stimulation and Ca(2+) release from the endoplasmic reticulum (ER). The protein that conveys the Ca(2+) content of the ER to the plasma membrane is the ER Ca(2+) sensor STIM1. STIM1 activates the Orai channels and is obligatory for channel opening. TRPC channels can function in two modes, as STIM1-dependent and STIM1-independent. When activated by STIM1, both channel types function at the ER/PM (plasma membrane) junctions. This chapter describes the properties and regulation of the channels by STIM1, with emphasis how and when TRPC channels function as STIM1-dependent and STIM1-independent modes and their unique Ca(2+)-dependent physiological functions that are not shared with the Orai channels.