Evidence for an essential role for calcium in excitation-contraction coupling in skeletal muscle

The events and processes that link the electrical events which occur at the surface of a muscle fibre with the contractile process that takes place within the fibre, have been a continuing source of interest. Recently attention has been concentrated on the role played by calcium ions in linking these two events. As often happens in physiological investigations, the idea that calcium ions play an essential role in excitation-contraction coupling is not new. As long ago as 1883 Ringer demonstrated that the frog heart fails to contract and remains relaxed when calcium ions are absent from its perfusion fluid. Later it was shown that under this condition the rhythmic spontaneous action potentials of this preparation are still present in an only slightly modified form (Mines 1913). It was known at that time that the depolarization of the muscle fibre membrane is the electrical event responsible for initiating the mechanical response (Biedermann 1896) and although this point has been disputed from time to time, the evidence presently available makes it obvious that this is the case. One explanation of these observations is that the action potential or depolarization permits or promotes the movement of calcium ions from the surface to the interior of the muscle fibre and that these ions then initiate the mechanical response. A working hypothesis of this type was proposed by Sandow (1952). However, until fairly recently the only direct evidence supporting such an hypothesis was the demonstration by Heilbrunn & Wiercinski (1947) that calcium was the only physiologically occurring cation which would cause shortening when injected into bits of skeletal muscle fibres in low concentrations. This effect was later confirmed under more physiological conditions by Niedergerke (1955). Although there is considerable evidence of recent origin showing that calcium ions play an essential role in coupling in smooth and cardiac muscles, for the sake of brevity attention will be concentrated on skeletal muscle in the present discussion.