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 nonexcitable cells, and the mechanisms linking the depletion of intracellular Ca²⁺ 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 Ca ²⁺ 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⁺ 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.