Cardiotoxins from cobra venoms: possible mechanisms of action

Alan L. Harvey

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

In addition to the postjunctional neurotoxins that bind to acetylcholine receptors, cobra venoms contain large quantities of similar polypeptides that act directly on cell membranes. These toxins ("cardiotoxins" "cytotoxins" "direct lytic factors" "membrane toxins" act in vivo to stop the heart in systole. They also cause depolarization and contracture of smooth and skeletal muscles, and depolarization of nerve cells. In higher concentrations, cardiotoxins lyse erythrocytes, an effect which is very pronounced in the presence of small amounts of phospholipase A2. There is no clear understanding of the mechanism of action of cardiotoxins. The nature of their binding site has not been elucidated, but high concentrations of Ca2+ prevent their binding to membranes. This, together with the basic nature of the toxins, implicates a negatively-charged membrane component. Despite the attractions of negatively-charged phospholipids found in studies with artificial membranes, such lipids are probably not important for the interaction of cardiotoxins with intact cells. Sialic acid residues are also unlikely to be part of the binding site, but membrane proteins have not been excluded. After binding has occurred, it is not likely that cardiotoxins cause a nonspecific lysis of the cell membrane, as previously postulated. Specific effects on enzyme such as Na+, K+-ATPase can also be ruled out. Rather, the toxins cause an increase in the permeability of membranes to small ions. It remains to be established whether this is because of a general "leakiness" after displacement of membrane-bound Ca2+, or because of the formation of oligomeric pores.

Original languageEnglish
Pages (from-to)41-69
Number of pages29
JournalToxin Reviews
Volume4
Issue number1
DOIs
Publication statusPublished - 1 Jan 1985

Keywords

  • cobra venoms
  • cardiotoxins
  • snake venom
  • blood and hemopoietic system
  • heart
  • hemolysis
  • human
  • membrane permeability
  • reptile
  • mechanisms

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