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1. For many years it has been known that when muscles are depolarized by raising [K+]out there is an increase in respiration, even at levels of depolarization below the threshold for a detectable contracture.
2. K+-stimulated respiration occurs in muscles in which protein synthesis is blocked with puromycin. Stimulation does not depend upon activation of phosphorylase kinase. In muscle poisoned with IIA and kept in N2, depolarizations below the threshold for contracture cause a fall in creatine phosphate. Apparently an ATPase is activated by depolarization; the resulting ADP is probably the trigger for the increase in oxygen uptake.
3. When the T-tubules are destroyed by the glycerol-osmotic shock method depolarization does not produce an increase in respiration.
4. Caffeine is known to stimulate respiration at concentrations below the threshold for producing a contracture. Muscles that have been made refractory to stimulation by potassium are still stimulated by caffeine: the action of caffeine is not antagonized by an increase in extracellular Mg2+. Caffeine must act on a later step in excitationcontraction coupling.
5. K+-stimulated respiration ultimately depends on the presence of Ca2+ in the Ringer. However, the Ca2+ can be replaced by Ni2+. It is known that Ni2+ does not activate actomyosin. Ni2+ is not sequestered by isolated fragments of the sarcoplasmic reticulum. It seems that the Ni2+ or Ca2+ in the extracellular solution is required for a superficial step in excitationcontraction coupling.
6. Respiration is also often stimulated when muscles are placed in an isotonic sucrose solution, even though the fibres are hyperpolarized. A trace amount of Ca2+ in the sucrose solution is probably necessary for the response.
7. An interaction between Ca2+ and a superficial membrane receptor appears to be an essential, early step in excitationcontraction coupling.
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