New and notable ion-channels in the sarcoplasmic/endoplasmic reticulum: do they support the process of intracellular Ca2+ release?

Intracellular Ca2+ release through ryanodine receptor (RyR) and inositol trisphosphate receptor (IP3R) channels is supported by a complex network of additional proteins that are located in or near the Ca2+ release sites. In this review, we focus, not on RyR/IP3R, but on other ion-channels that are known to be present in the sarcoplasmic/endoplasmic reticulum (ER/SR) membranes. We review their putative physiological roles and the evidence suggesting that they may support the process of intracellular Ca2+ release, either indirectly by manipulating ionic fluxes across the ER/SR membrane or by directly interacting with a Ca2+-release channel. These channels rarely receive scientific attention because of the general lack of information regarding their biochemical and/or electrophysiological characteristics makes it difficult to predict their physiological roles and their impact on SR Ca2+ fluxes. We discuss the possible role of SR K+ channels and, in parallel, detail the known biochemical and biophysical properties of the trimeric intracellular cation (TRIC) proteins and their possible biological and pathophysiological roles in ER/SR Ca2+ release. We summarise what is known regarding Cl- channels in the ER/SR and the non-selective cation channels or putative 'Ca2+ leak channels', including mitsugumin23 (MG23), pannexins, presenilins and the transient receptor potential (TRP) channels that are distributed across ER/SR membranes but which have not yet been fully characterised functionally.