Type 3 inositol 1,4,5-trisphosphate receptor and capacitative calcium entry
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Updated: Feb 6, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
1Calcium Regulation Section, National Institute of Environmental Health Sciences-NIH, Research Triangle Park, North Carolina 27709, USA. Putney@niehs.nih.gov
Abstract:
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)IP3} receptor can also function as a capacitative calcium entry channel, specifically: (i) in some cell types, the properties of Ca2+ store depletion-activated currents and channels resemble those of an (1,4,5)IP3 receptor;(ii) in these same cell types, (1,4,5)IP3 directly activates channels in the plasma membrane (including in one study, the same channels activated by depletion of Ca2+ 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 Ca2+ 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 IP3 and trp protein families, this may represent an example of convergent evolution of function.
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