Binding of the sea anemone polypeptide BDS II to the voltage-gated sodium channel.

BDS II, a 43-residue polypeptide from the sea anemone Anemonia sulcata, is reported to have both antihypertensive and antiviral activity. This polypeptide possesses a number of sequence and structural similarities to a class of cardiotonic proteins which bind to receptor site 3 of the voltage-gated sodium channel. In contrast to these cardiostimulant proteins, which produce positive inotropic effects at concentrations of 2-15 nM, BDS II produced a weak negative inotropic effect upon isolated guinea-pig atria, with doses of 90 and 180 nM depressing contractile strength by 15 and 28%, respectively. BDS II also competed with a 125-iodine labelled derivative of AP-A (a representative of the cardiostimulant proteins) bound to sodium channels in rat brain synaptosomes. The IC50 for BDS II versus AP-A was 5.2 microM. BDS II may therefore be considered an antagonist for receptor site 3 of the voltage-gated sodium channel. Structural differences between BDS II and the agonist AP-A which may give rise to their different effects on the sodium channel are considered.