ABSTRACT
The most commonly prescribed of the positive inotropes is the cardiac glycoside digoxin. Digitalis toxicity is manifest in CNS side-effects such as fatigue, visual disturbances, and anorexia, and in cardiac side-effects that depend on the nature and extent of the underlying heart disease. The polypeptide ATX II has been found to have class II antianhythmic activity, indicating its potential in the management of cardiac arrhythmias. Information about which residues are essential for the cardiac stimulatory activity of the sea anemone toxins has been obtained from selective chemical modification and proteolysis studies, comparisons among naturally occurring sequences, and, most recently, site-directed mutagenesis. It is also interesting that in ATX Ia, which is a potent crustacean neurotoxin but a poor mammalian cardiac stimulant, Lys37 and both histidines are missing, suggesting that one or more of these side chains may be important in promoting specificity for the mammalian cardiac sodium channel.
