CALSEQUESTRIN IS ESSENTIAL FOR THE CA2-ALPHA IN SKELETAL-MUSCLE SARCOPLASMIC-RETICULUM( RELEASE INDUCED BY MYOTOXIN)

Myotoxin alpha (MYTX), a polypeptide toxin purified from the venom of prairie rattlesnakes (Crotalus viridis viridis), induced Ca2+ release from the heavy fraction of skeletal sarcoplasmic reticulum (HSR), usin g a Ca2+ electrode. The effect of MYTX was nearly abolished by pretrea tment with ryanodine, an alkaloid-based Ca2+ channel blocker. In the s topped-flow experiments, MYTX increased the choline(+) permeability of HSR in the presence of calsequestrin (CS). Single channel recording e xperiments showed that in the presence of CS, the channel currents wer e markedly enhanced by MYTX applied to the cis side, but not to the tr ans side. However, in the absence of CS, MYTX failed to cause the exci tatory effect in both the experiments. These results suggest that CS i s essential for MYTX-induced Ca2+ release through the Ca2+ release cha nnels in skeletal HSR.