Sigma-ligands comprise several chemically unrelated drugs such as haloperidol, pentazocine, and ditolylguanidine, which bind to a family of low molecular mass proteins in the endoplasmic reticulum.

Production of active force in skeletal muscle results from the interaction of myosin-containing thick filaments with actin-containing thin filaments. These muscles are also passively elastic, producing forces that resist stretch independently of ATP splitting or of interaction between the filaments. The mechanism of this passive elasticity is unknown; suggestions include gap filaments in the region between thick and thin filaments in muscles stretched beyond filament overlap, or intermediate filaments which connect successive Z-disks. Recently, the two exceptionally large proteins titin (also called connectin) and nebulin (originally called band 3) have been implicated in passive elasticity (for review see refs 7, 8). Here, we show that after these proteins are degraded by low doses of ionizing radiation, the ability of single skinned muscle cells to generate both passive tension in response to stretch and active tension in response to calcium is greatly reduced. These effects are accompanied by axial misalignment of thick filaments. Titin and/or nebulin apparently provide axial continuity for the production of resting tension on stretch and also tend to keep the thick filaments centred within the sarcomere during force generation.

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