Ca2+ loading reduces the tensile strength of sarcolemmal vesicles shed from rabbit muscle.

1. Sarcolemmal vesicles shed by rabbit muscle were loaded with Ca2+ by means of A23187 or ionomycin. [Ca2+]0 was buffered between 0.8 and 20 microM. Membrane strength was measured by pipette aspiration. 2. At 20 microM Ca2+ many vesicles underwent autolysis, or were so weak that they burst instantly on aspiration. Between 10 and 2 microM Ca2+ a graded decrease in membrane strength was demonstrable. At 0.8 microM Ca2+ the mechanical properties of the sarcolemma remained unaltered. 3. Mg2+ carried by A23187 does not mimic the effect of Ca2+. The ionophore itself similarly did not cause a decrease in membrane tensile strength. 4. Pre‐treatment with BAPTA‐AM, so as to buffer internal Ca2+, partly protected vesicles against the decrease in membrane strength produced by Ca2+ loading. 5. Membrane strength was not restored by adding excess BAPTA to the bathing solution, so as to reverse the Ca2+ gradient. An irreversible degradation of the membrane consequent upon raised [Ca2+]1 seems indicated. 6. These findings are discussed in relation to the mechanisms which have been advanced to account for the role of elevated [Ca2+]1 in cell death. 7. An attempt to use staphylococcal alpha‐toxin as an alternative means to permeabilize the sarcolemma led to the incidental finding that this pore‐forming protein itself greatly weakens the membrane in doses lower than required for effective permeabilization.