InsP₃R channel gating altered by clustering?

Abstract

Arising from T. Rahman, A. Skupin, M. Falcke & C. W. Taylor Nature 458, 655–659 (2009)10.1038/nature07763

The inositol trisphosphate receptor (InsP₃R) forms a calcium channel that resides in the membrane of the endoplasmic reticulum and is activated by inositol trisphosphate (InsP₃). InsP₃ is a phosphorylated monosaccharide that is generated via hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, and activation of the InsP₃R is involved in a broad range of biological processes, including cell division, apoptosis and development. Rahman et al.^1,2 reported that exposure to low concentrations of InsP₃ induces rapid clustering of InsP₃R Ca²⁺ release channels normally randomly distributed in endoplasmic reticulum/outer nuclear membranes. Importantly, clustered channels gate differently from lone channels. Using similar protocols, we observed InsP₃R channel clustering without exposure to InsP₃ (Fig. 1a), as we found in other systems^3,4,5 with protocols designed to avoid InsP₃ pre-exposure. More significantly, we find that clustering has no effect on InsP₃R channel gating. For this reason, we believe that InsP₃-induced channel clustering and modification of channel gating by clustering may not be universal phenomena.