New and notable ion-channels in the sarcoplasmic/endoplasmic reticulum: do they support the process of intracellular Ca~2+ release?

摘要

Intracellular Ca~2+ release through ryanodine receptor (RyR) and inositol trisphosphatereceptor (IP3R) channels is supported by a complex network of additional proteins that arelocated in or near the Ca~2+ release sites. In this review, we focus, not on RyR/IP_3R, but on otherion-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 theymay support the process of intracellular Ca~2+ release, either indirectly by manipulating ionicfluxes across the ER/SR membrane or by directly interacting with a Ca~2+-release channel. Thesechannels rarely receive scientific attention because of the general lack of information regardingtheir biochemical and/or electrophysiological characteristics makes it difficult to predict theirphysiological roles and their impact on SR Ca~2+ fluxes. We discuss the possible role of SR K~+channels and, in parallel, detail the known biochemical and biophysical properties of the trimericintracellular cation (TRIC) proteins and their possible biological and pathophysiological roles inER/SR Ca~2+ release. We summarise what is known regarding Cl~ channels in the ER/SR and thenon-selective cation channels or putative 'Ca~2+ leak channels', including mitsugumin23 (MG23),pannexins, presenilins and the transient receptor potential (TRP) channels that are distributedacross ER/SR membranes but which have not yet been fully characterised functionally.