Calcium ion as a second messenger with special reference to excitation-contraction coupling

Calcium ion (Ca(2+)) plays an important role in stimulus-response reactions of cells as a second messenger. This is done by keeping cytoplasmic Ca(2+) concentration low at rest and by mobilizing Ca(2+) in response to stimulus, which in turn activates the cellular reaction. The role of Ca(2+) as a second messenger was first discovered in excitation-contraction coupling of skeletal muscle. The history of the discovery was reviewed. Characteristics of Ca(2+) as a second messenger, diversity of target molecules, capability of rapid and massive mobilization and also of oscillatory mobilization, tendency toward localization, and on the other side, ability to cause generalized cell response were described. The possible bases for these characteristics was discussed. Ca(2+) itself induces release of Ca(2+) from the sarcoplasmic reticulum (Ca(2+)-induced Ca(2+) release [CICR]). The Ca(2+) release channel, ryanodine receptor, incorporated into lipid bilayer shows CICR activity. Ca(2+) release induced by inositol trisphosphate also has an apparent CICR nature. The significance of CICR or apparent CICR with its inherently regenerative nature in physiological contractions of skeletal, cardiac, and smooth muscles was discussed.