Type 3 inositol 1,4,5-trisphosphate receptor and capacitative calcium entry

It is well established that depletion of intracellular stores of calcium can activate calcium influx across the plasma membrane, a process known as ‘capacitative calcium entry’. Recent research and reviews have focussed on homologs of the Drosophila mutant, trp, as candidates for the channels underlying this phenomenon. However, there is recent evidence that the type 3 inositol 1,4,5-trisphosphate {(1,4,5)IP 3} receptor can also function as a capacitative calcium entry channel, specifically: (i) in some cell types, the properties of Ca 2+ store depletion-activated currents and channels resemble those of an (1,4,5)IP 3 receptor; (ii) in these same cell types, (1,4,5)IP 3 directly activates channels in the plasma membrane (including in one study, the same channels activated by depletion of Ca 2+ stores); and (iii) expression of the type 3 receptor in Xenopus oocytes resulted in the association of this receptor with the plasma membrane, and facilitation of Ca 2+ entry across the plasma membrane. The type 3 receptor may represent one type of capacitative calcium entry channel expressed in some cell types and, in other cell types, channels with markedly different properties (i.e. trp) may carry out this function. Furthermore, as there is little, if any, homology between the IP 3 and trp protein families, this may represent an example of convergent evolution of function.