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 activity of frog heart atrial muscle preparations. The peak tension of isolated trabeculae was sensitive to nanomolar concentrations of Bistramide A. Lineweaver-Burk relationships suggest that Bistramide A competes with Ca for a common site. In voltage-clamped trabeculae, the toxin inhibited both the cadmium-sensitive Ca current and the phasic component of the tension with a dissociation constant of 3.3 microM and a stoichiometry 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 activated force and decreased the sensitivity of the contractile proteins to Ca. The data suggest that Bistramide A decreases the Ca-sensitivity of contractile proteins prior to blocking the Ca current.