DOES THE PROTEIN-KINASE-C PATHWAY MODULATE SARCOLEMMA DAMAGE AND THE RELEASE OF CYTOSOLIC PROTEINS IN THE RAT-HEART

1. The release of creatine kinase (CK) in the Langendorff-perfused rat heart during the Ca2+-paradox, was critically dependent on the durati on and [Ca2+]. of the initial Ca2+-depletion phase. 2. When [Ca2+]i wa s raised by perfusion with caffeine or under N2, activation of the pro tein kinase C pathway (PKC) produced a small but significant release o f CK. PKC stimulation is therefore able to substitute for the Ca2(o)2-depletion of the Ca2+-paradox. 3. The PKC inhibitor, 1-(5-isoquinolin yl sulphonyl)-2-methyl piperazine, (2 x 10(-6)M) inhibited both the Ca 2+-paradox and caffeine-induced release of CK. 4. It is concluded that the PKC pathway has a regulatory role for the damage system of the sa rcolemma that is responsible for the release of cytosolic proteins.