Bistramide A, a new toxin isolated from the Urochordate Lissoclinum bi
stratum Sluiter, was applied to rat auricular heart muscle bundles. At
a stimulation frequency of 0.2 Hz, the toxin induces a dose-dependent
reduction of the stimulated twitch tension force; it decreases V-max
and shortens the duration of the plateau and the slow repolarizing pha
se of the action potential. In the control solution, switching from a
stimulation frequency of 0.2 Hz to 1 Hz decreases the force with which
a positive potentiation develops either at a maintained high frequenc
y or after switching from 1 Hz to 0.2 Hz. Bistramide A reduces both th
e force evoked at 1 Hz and the potentiation. The data suggest that Bis
tramide A blocks Na+ conductance; inhibits Ca++ channels in a time-and
frequency-dependent manner; reduces Na+-Ca++ exchange activity; but d
oes not modify the ability of the sarcoplasmic reticulum to be refille
d although the rate of Ca++ accumulation is decreased.