Orai channel-mediated Ca²⁺ signals in vascular and airway smooth muscle

Orai (Orai1, Orai2, and Orai3) proteins form a family of highly Ca²⁺-selective plasma membrane channels that are regulated by stromal-interacting molecules (STIM1 and STIM2); STIM proteins are Ca²⁺ sensors located in the membrane of the endoplasmic reticulum. STIM and Orai proteins are expressed in vascular and airway smooth muscle and constitute the molecular components of the ubiquitous store-operated Ca²⁺ entry pathway that mediate the Ca²⁺ release-activated Ca²⁺ current. STIM/Orai proteins also encode store-independent Ca²⁺ entry pathways in smooth muscle. Altered expression and function of STIM/Orai proteins have been linked to vascular and airway pathologies, including restenosis, hypertension, and atopic asthma. In this review we discuss our current understanding of Orai proteins and the store-dependent and -independent signaling pathways mediated by these proteins in vascular and airway smooth muscle. We also discuss the current studies linking altered expression and function of Orai proteins with smooth muscle-related pathologies.