Publisher Summary This chapter discusses the theory of muscle contraction. According the theory of contraction— the sliding filament theory—contraction is the result of the myofilaments sliding over one another, that is, it is a consequence of increased interdigitation of the myofilaments. In a muscle at its relaxed resting length, about two-thirds of the length of each thick filament and about half of that of each thin filament are overlapped. The process of contraction is a consequence of the formation of cross-bridges between the globular heads of the thick myosin filaments and the G actin units of the thin filaments. The cross-bridges are rapidly formed and broken, each detaching itself from one site on the thin filament and reattaching itself to another site further along and so on, with the result that the thin filament slides along the thick filament, like a line of men pulling in a rope hand over hand. Relaxation to the resting muscle length occurs because cross-bridges cease to be formed, allowing the filaments to readjust to the resting degree of interdigitation. Drugs may increase or decrease the contractions of striated muscle by affecting one or more of the processes in the excitation–contraction coupling sequence. The ultimate cause of the altered contractility is usually a change in the rate of Ca release from, in the amount of Ca2+ released from or in the rate of Ca2+ reuptake by, the sarcoplasmic reticulum.