Pharmacological evaluation of early afterdepolarisations induced by sea anemone toxin (ATXII) in dog heart.
OBJECTIVE
ATXII is a polypeptide toxin isolated from the sea anemone, Anemonia sulcata, known to delay sodium inactivation markedly and to induce early afterdepolarisations. The aim was to investigate the mechanism of its action.


METHODS
The mechanism of ATXII induced early afterdepolarisations was investigated in vitro in canine endocardial preparations using standard microelectrode techniques.


RESULTS
ATXII (2 x 10(-7) M) induced cycle length dependent prolongation of plateau, more marked in Purkinje than in muscle fibres, and early afterdepolarisations in Purkinje fibres only. The calcium channel antagonists verapamil (10(-6) M, 10(-5) M) and cobalt (2-4 mM), and drugs that block calcium release from the sarcoplasmic reticulum, ryanodine (10(-6) M, 10(-5) M) and caffeine (10 mM), did not antagonise the ATXII effects. However, tetrodotoxin (5 x 10(-6) M) and lignocaine (4 x 10(-5) M) shortened the action potential and suppressed early afterdepolarisations. The effects of lignocaine were seen at concentrations that did not significantly affect Vmax.


CONCLUSIONS
ATXII induced early after depolarisations are due to the effects of ATXII on Na+ entry, probably via a slowly inactivated Na+ channel population. Calcium entry through the sarcolemmal Ca2+ channels and cyclic Ca2+ release from the sarcoplasmic reticulum are not required for the genesis of early afterdepolarisations in this model.
Boutjdir
M
M
Cardiology Division (111), Veterans Administration Medical Center (State University of New York), Brooklyn 11209.
el-Sherif
N
N
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003064:Cnidarian Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D046508:Culture Techniques; D004285:Dogs; D004558:Electric Stimulation; D004699:Endocardium / Q000187:drug effects* / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012615:Sea Anemones; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
D015220:Calcium Channels; D002316:Cardiotonic Agents; D003064:Cnidarian Venoms; D015222:Sodium Channels; C028800:toxin II (Anemonia sulcata)