Phosphoinositides in Ca2+ signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers

摘要

Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) would be critical for skeletal muscle excitation-contraction (EC) coupling, the issue of whether phosphoinositides (PtdInsPs) may have something to do with Ca2+ signaling in muscle raised limited interest, if any. In recent years however, the PtdInsP world has expanded considerably with new functions for PtdIns(4,5)P-2 but also with functions for the other members of the PtdInsP family. In this context, the discovery that genetic deficiency in a PtdInsP phosphatase has dramatic consequences on Ca2+ homeostasis in skeletal muscle came unanticipated and opened up new perspectives in regards to how PtdInsPs modulate muscle Ca2+ signaling under normal and disease conditions. This review intends to make an update of the established, the questioned, and the unknown regarding the role of PtdInsPs in skeletal muscle Ca2+ homeostasis and EC coupling, with very specific emphasis given to Ca2+ signals in differentiated skeletal muscle fibers.