Potassium-stimulated respiration and intra-cellular calcium releae in from skeletal muscle.

1. In 1931 Fenn showed that the respiration of frog twitch muscles increases when [K(+)](o) is raised. The present paper is a further study of potassium-stimulated respiration. Stimulation depends on membrane potential, since respiration is also stimulated by elevated [Rb(+)](o) or [Cs(+)](o) in direct relation to their ability to depolarize.2. When [K(+)](o) is elevated to 25 mM there is an increase in respiration which is sustained for hours. If [K(+)](o) is 30 mM or above, there is a transitory burst of stimulated respiration, followed by a decline back to the basal level.3. If [K(+)](o) is raised in steps from 20 to 30 mM, there may never be a burst of increased oxygen consumption. Often a rise in [K(+)](o) from 20 to 24 mM decreases respiration.4. The response to elevated [K(+)](o) can be blocked by divalent cations or by local anaesthetics; the blocking agents do not interfere with the depolarization of the membrane. The blocking agents act rapidly; they probably take effect soon after they contact the cell membrane.5. Either extracellular Ca(2+) or Sr(2+) is important for the stimulation of respiration. The burst produced by 50 mM [K(+)](o) is transformed into a sustained rise in respiration when [Ca(2+)](o) or [Sr(2+)](o) are also raised. If a muscle is stimulated with 25 mM [K(+)](o) in the absence of extracellular calcium, respiration is elevated as usual, but now the rise is transitory unless Ca(2+) or Sr(2+) are added back to the extracellular solution.6. Depolarization seems to stimulate respiration by causing the release of Ca(2+) into the sarcoplasm. Since respiration is increased by a depolarization below the threshold for producing a contracture, respiration is more sensitive than contraction as an indicator of sarcoplasmic calcium concentration.7. A model for the relation between sarcoplasmic calcium and membrane potential is proposed. The model accounts for the time course of the stimulation of respiration and also for much of the available data on potassium contracture. In the model, Ca(2+) is released into the sarcoplasm from a store in the cell. With depolarization, the release of Ca(2+) from the store is increased, but the rate at which extracellular Ca(2+) can replenish the store is decreased. The ability of the longitudinal reticulum to pump Ca(2+) from the sarcoplasm does not vary with membrane potential.