The Complex Role of Store Operated Calcium Entry Pathways and Related Proteins in the Function of Cardiac, Skeletal and Vascular Smooth Muscle Cells

Abstract

Cardiac, skeletal, and smooth muscle cells shared the common feature of contraction in response to different stimuli. Agonist-induced muscle's contraction is triggered by a cytosolic free Ca2+ concentration increase due to a rapid Ca2+ release from intracellular stores and a transmembrane Ca2+ influx, mainly through L-type Ca2+ channels. Compelling evidences have demonstrated that Ca2+ might also enter through other cationic channels such as Store-Operated Ca2+ Channels (SOCCs), involved in several physiological functions and pathological conditions. The opening of SOCCs is regulated by the filling state of the intracellular Ca2+ store, the sarcoplasmic reticulum, which communicates to the plasma membrane channels through the Stromal Interaction Molecule 1/2 (STIM1/2) protein. In muscle cells, SOCCs can be mainly non-selective cation channels formed by Orai1 and other members of the Transient Receptor Potential-Canonical (TRPC) channels family, as well as highly selective Ca2+ Release-Activated Ca2+ (CRAC) channels, formed exclusively by subunits of Orai proteins likely organized in macromolecular complexes. This review summarizes the current knowledge of the complex role of Store Operated Calcium Entry (SOCE) pathways and related proteins in the function of cardiac, skeletal, and vascular smooth muscle cells.

TRPC channels: Dysregulation and Ca²⁺ Mishandling In Ischemic Heart Disease

“…TRPC1,3,4,5 and 6 are upregulated in mouse and rat animal models of MI [5,13,63]. Compelling evidence indicates TRPC channel overexpression contribute to Ca 2+ entry, mediating the activation of Ca 2+ sensitive signaling pathway, as calcineurin-NFAT, a critical pathway involved in apoptosis, cardiac hypertrophy and fibrosis [13,19,27,34,61]. TRPC proteins are likely involved also in cardiac repair related processes.…”

“…Although, the induced stress-stimulated contractility, known as the Anrep effect, is diminished in isolated papillary muscles and cardiomyocytes from TRPC6 KO, but not TRPC3 KO mice [59]. In [13,19,27,34,61]. Here, we will discuss the role of TRPC channels in processes related to cardiac ischemic diseases.…”

TRPCs: Influential Mediators in Skeletal Muscle

“…TRPCs are known to participate in various physiological and pathophysiological events in skeletal muscle, as briefly summarized in Figure 1. Concerning a comparison of TRPC-mediated SOCE or Ca 2+ -entry in skeletal, cardiac or smooth muscle SOCE, please refer to recent review articles [64,76,114,115].…”

“…To compare Orai1-mediated skeletal SOCE and cardiac or smooth muscle SOCE, please refer to a recent brief review article [64].…”

Priority Strategy of Intracellular Ca2+ Homeostasis in Skeletal Muscle Fibers during the Multiple Stresses of Hibernation

“…Stromal interaction molecule-1 (STIM1) located in the endoplasmic reticulum (ER) and Orai1 (also known as calcium-release-activated calcium-modulator, CRACM1) located in the cell membrane are two essential components required for SOCE [8][9][10]. With external stimulation, Ca 2+ is released from the STIM1 EF-hand domain, which triggers the aggregation and movement of STIM1 to ER/plasma membrane (PM) binding sites, as well as the Orai1 aggregation of STIM1, and leads to the activation of SOCE and Ca 2+ influx [11][12][13][14]. The ryanodine receptor (RyR) is a major SR Ca 2+ release channel.…”