Calcium ionophore A23187 potentiates twitch and intracellular calcium release in single muscle fibres

Abstract

THE potentiation by drugs of the twitch force in skeletal muscle has generally been related to a prolongation of the ‘active state’ in the excitation–contraction coupling mechanisms1,2. This can, however, only be partially correct since in another type of potentiation elicited by repetitive stimulation (staircase phenomenon), the ‘active state’ was found to be intensified but not prolonged3. This view that the ‘active state’ is not maximum in a single twitch and that it can indeed be intensified in twitch potentiation was criticised4 but subsequently received support from several studies5,6. On the other hand it is well known that activation of muscle contraction involves rapid changes of the intracellular calcium concentration which result from calcium release and uptake processes in the sarcoplasmic reticulum (SR)7,8. The discovery of specific ionophores (antibiotics allowing cations to cross biological membranes by way of a fairly electroneutral mechanism) which selectively increase the membrane permeability to calcium9–11 offers a new tool for probing these intramuscular processes. For example, ionophore X537A was found to alter the contractile responses and resting tension of strips of rat diaphragm, an effect which was ascribed primarily to an increased calcium influx across the muscle fibre membrane12. On the other hand the ionophores X537A and A23187 tested on SR vesicles and mitochondria isolated by ultracentrifugation were found to induce a release of stored calcium10,12,13.