Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) 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)P2 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.
- Calcium homeostasis
- Excitation–contraction coupling
- Ryanodine receptor
- Sarcoplasmic reticulum Ca release
- Skeletal muscle fibers
ASJC Scopus subject areas
- Cell Biology