CALCIUM-GATED CALCIUM CHANNELS IN SARCOPLASMIC-RETICULUM OF RABBIT SKINNED SKELETAL-MUSCLE FIBERS

The action of ruthenium red (RR) on Ca2+ loading by and Ca2+ release from the sarcoplasmic reticulum (SR) of chemically skinned skeletal muscle fibers of the rabbit was investigated. Ca2+ loading, in the presence of the precipitating anion pyrophosphate, was monitored by a light-scattering method. Ca2+ release was indirectly measured by following tension development evoked by caffeine. Stimulation of the Ca2+ loading rate by 5 .mu.M RR was dependent on free Ca2+, being maximal at pCa 5.56. Isometric force development induced by 5 mM caffeine was reversibly antagonized by RR. IC50 for the rate of tension rise was 0.5 .mu.M; that for the extent of tension was 4 .mu.M. RR slightly shifted the steady state isometric force/pCa curve toward lower pCa values. At 5 .mu.M RR, the pCa required for half-maximal force was 0.2 log units lower than that of the contol, and maximal force was depressed by .apprx. 16%. These results suggest that RR inhibited Ca2+ release from the SR and stimulated Ca2+ loading into the SR by closing Ca2+-gated Ca2+ channels. Previous studies on isolated SR have indicated the selective presence of such channels in junctional terminal cisternae.