Calcium-gated Calcium Channels

The action of ruthenium red (RR) on Ca" loading by and Ca" release from the sarcoplasmic reticulum (SR) of chemically skinned skeletal muscle fibers of the rabbit was investigated . Ca" loading, in the presence of the precipitating anion pyrophosphate, was monitored by a light-scattering method . Ca" release was indirectly measured by following tension development evoked by caffeine . Stimulation of the Ca" loading rate by 5 UM RR was dependent on free Ca", 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 uM ; that for the extent of tension was 4 AM. RR slightly shifted the steady state isometric force/pCa curve toward lower pCa values . At 5 jM RR, the pCa required for half-maximal force was 0.2 log units lower than that of the control, and maximal force was depressed by ^-16% . These results suggest that RR inhibited Ca2' release from the SR andstimulated Ca21 loading into the SR by closing Ca2'-gated Ca21 channels . Previous studies on isolated SR have indicated the selective presence of such channels in junctional terminal cisternae.