THE POLYETHER BISTRAMIDE-A AFFECTS THE CALCIUM SENSITIVITY OF THE CONTRACTILE PROTEINS IN FROG ATRIAL HEART-MUSCLE

The effects of Bistramide A, a new toxin isolated from the Urochordate Lissoclinum bistratum Sluiter have been studied on the mechanical act ivity of frog heart atrial muscle preparations. The peak tension of is olated trabeculae was sensitive to nanomolar concentrations of Bistram ide A. Lineweaver-Burk relationships suggest that Bistramide A compete s with Ca for a common site. In voltage-clamped trabeculae, the toxin inhibited both the cadmium-sensitive Ca current and the phasic compone nt of the tension with a dissociation constant of 3.3 muM and a stoich iometry of 2. Bistramide A decreased the isometric tension of skinned fibres in a dose-dependent manner with a dissociation constant of 400 nM and a stoichiometry of 2. The toxin reduced the maximum Ca activate d force and decreased the sensitivity of the contractile proteins to C a. The data suggest that Bistramide A decreases the Ca-sensitivity of contractile proteins prior to blocking the Ca current.