Sigma-1 Receptor - Functions

Functions

A variety of specific physiological functions have been attributed to the sigma-1 receptor. Chief among these are modulation of Ca2+ release, modulation of cardiac myocyte contractility, and inhibition of voltage gated K+ channels. The reasons for these effects are not well understood, even though sigma-1 receptors have been linked circumstantially to a wide variety of signal transduction pathways. Links between sigma-1 receptors and G-proteins have been suggested such as sigma-1 receptor antagonists showing GTP-sensitive high affinity binding, there is also, however, some evidence against a G-protein coupled hypothesis. The sigma-1 receptor has been shown to appear in a complex with voltage gated K+ channels (Kv1.4 and Kv1.5), leading to the idea that sigma-1 receptors are auxiliary subunits. Sigma-1 receptors apparently co-localize with IP3 receptors on the endoplasmic reticulum. Also, sigma-1 receptors have been shown to appear in galactoceramide enriched domains at the endoplasmic reticulum of mature oligodendrocytes. The wide scope and effect of ligand binding on sigma-1 receptors has led some to believe that sigma-1 receptors are intracellular signal transduction amplifiers.

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