Role of TRPC Channels in Store-Operated Calcium Entry

Abstract

Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of Ca(2+) stores within the endoplasmic reticulum (ER) and contributes to the control of various physiological functions in a wide variety of cell types. The transient receptor potential canonical (TRPC) channels (TRPCs 1-7), that are activated by stimuli leading to PIP2 hydrolysis, were first identified as molecular components of SOCE channels. TRPC channels show a miscellany of tissue expression, physiological functions and channel properties. However, none of the TRPC members display currents that resemble I CRAC. Intensive search for the CRAC channel component led to identification of Orai1 and STIM1, now established as being the primary constituents of the CRAC channel. There is now considerable evidence that STIM1 activates both Orai1 and TRPC1 via distinct domains in its C-terminus. Intriguingly, TRPC1 function is not only dependent on STIM1 but also requires Orai1. The critical functional interaction between TRPC1 and Orai1, which determines the activation of TRPC1, has also been identified. In this review, we will discuss current concepts regarding the role of TRPC channels in SOCE, the physiological functions regulated by TRPC-mediated SOCE, and the complex mechanisms underlying the regulation of TRPCs, including the functional interactions with Orai1 and STIM1.

Relaxing Effect of TSU-68, an Antiangiogenic Agent, on Mouse Airway Smooth Muscle

“…TRPC channels, which are important components of NSCC, played critical roles in mediating extracellular Ca 2+ influx [48-52]. To further identify the NSCCs involved in TSU-68-blocked Ca 2+ influx at the molecular level, the TRPC3 inhibitor Pyr3 [44, 53] and gadolinium, which is a blocker of TRPC1, 3, 5, 6, and 7 [54], were applied sequentially.…”

Transient Receptor Potential (TRP) Channels

“…TRPC channels have been shown to form both heterotetramers and homotetramers within the TRP channel superfamily, with different members having certain preferences, for example, TRPC1 forms physiologically relevant functional channels with several TRPC channels including TRPC4, as well as, TRPV1, and TRPP2 (Ong et al 2016; Dietrich et al 2014). …”

“…As mentioned previously, TRPC1 was originally discovered as a potential store-operated Ca 2+ channel, but characterization of this channel did not show it to have the predicted traits of a store operated Ca 2+ channel or I CRAC activity (Ong et al 2016). Still, TRPC1 has been shown to be involved in store-operated Ca 2+ entry (SOCE) through its interactions with Orai1 and STIM1 thus designating it as having I SOC activity (Ong et al 2016).…”

“…Still, TRPC1 has been shown to be involved in store-operated Ca 2+ entry (SOCE) through its interactions with Orai1 and STIM1 thus designating it as having I SOC activity (Ong et al 2016). SOCE is a signaling cascade that is critical for an abundance of biological processes.…”

“…When Ca 2+ is released from the endoplasmic reticulum the cytosolic Ca 2+ concentration increases which triggers activation of plasma membrane Ca 2+ channels ( I CRAC or I SOC ). Evidence suggests that TRPC1 colocalizes with STIM1 and Orai1 in endoplasmic reticulum-plasma membrane (EM-PM) junctions wherein these two membranes exist in close proximity to one another (Ong et al 2016). Orai1 has been shown to be necessary for TRPC1 activation, though different splice variants of TRPC1 seem to be modulated by Orai1 differently (Ong et al 2016).…”