New aspects of the mechanism of Ca2+ entry in non-excitable cells

Abstract

The capacitative Ca2+ entry has been accepted to play a crucial role in Ca2+ signaling in non-excitable cells, and the mechanisms linking the depletion of intracellular Ca2+ stores to the activation of Ca2+ entry are presently the subject of intensive investigation. There are two hypotheses to explain the molecular mechanism of capacitative Ca2+ entry. One is that a diffusible second messenger released from intracellular Ca2+ stores may activate a Ca2+ channel at the plasma membrane. Numerous molecules, including CIF, cGMP, arachidonic acid, and a small G-protein, are proposed as the candidates for the diffusible messenger. In addition, the capacitative Ca2+ entry has been suggested to be modulated by protein phosphorylation/dephosphorylation. Another hypothesis is termed the "conformational coupling model". This model suggests that information between the IP3 receptor and a plasma membrane Ca2+ channel may be transferred directly through conformational protein-protein interactions. The plasma membrane Ca2+ channel involved in the capacitative Ca2+ entry is still neither purified nor cloned, but recent studies suggest that the mammalian homologue of the Drosophila protein Trp may function as a capacitative Ca2+ entry channel.