Toward an understanding of the regulation of myofibrillar function

Regulation of muscle contraction has been viewed as principally involving Ca(2+) binding to regulatory proteins on the thin filament, but while this is an important element of regulation, the mechanism does not explain the precise matching of muscle performance to the load it must lift or move. Now, it is increasingly evident that mechanisms instrinsic to the thick filament activate myosin cross-bridges as the force or load on a muscle increases. Both thick and thin filament regulatory mechanisms are featured in this special issue of the Journal of General Physiology.