MYOTOXINS and CARDIOTOXINS  

Cytolytic or Hemolytic?

Whereas many, if not all, toxic venom enzymes can prove to be toxic to muscle during envenomation there are also toxins that have been determined as specific myotoxins. These are basically cytotoxins that cause damage to muscle cells. Many cardiotoxins are cytotoxins that have been found to exert specific damage to cardio cells.   The toxin that is cytolytic is certainly also hemolytic. A hemolytic or cytolytic toxin certainly has potential as a myotoxin or cardiotoxin.

Neurotoxins

It has already been discussed that the lethality of some snake venoms is not contributed to enzymes, but rather to other polypeptides that are devoid of enzymatic activity. There are also polypeptide neurotoxins termed curare-mimetic toxins or postsynaptically acting neurotoxins that blocks acetylcholine to receptors at the neuromuscular junctions at the heart side of the synapse. However, the greatest effects of these toxins are generally exerted on respiratory muscles. They interfere with the reception of acetycholine on nicotinic receptors at the neuromuscular junctions.

Presynaptic neurotoxins also have a similar end effect on muscle contraction, as do the postsynaptic neurotoxins, but take a different path that blocks the transmissions of acetylcholine by prejunctional blocking before the synapse. The nerve signal transmission, in most cases is reduced or never reaches the receptor. Three groups of presynaptic neurotoxins are known. The Phospholipase A 2   (PLA 2- toxins), the dendrotoxins and the fasciculins, (anticholinesterase toxins) . The later two groups are only found within the mamba, dendropsis species. All elapid venoms, hydrophid, and some crotalid and viperid share the group of PLA 2 –toxins.   The actions of most neurotoxins can be explained in general as acting either in competitive inhibition, targeting and blocking receptor sites or by preventing release of acetylcholine. This results in muscular paralysis. Though presynaptic and postsynaptic toxins are devoid of substantial enzymatic activity, it should be noted  there are enzymes present  in the venom that aids in facilitating the spread of these toxins.

he dendrotoxins and fasciculins, contrary to blocking the receptors or by reducing the release of acetylcholine, as with all other neurotoxins, facilitate release of acetylcholine and augment responses to nerve stimulation in amplitude and duration. A note should be added here that the content of mamba venom varies between the four species. D. polylepis, D. viridis and D. jamesonii also contain potent postsynaptic neurotoxins, whereas,  D. angusticeps does not. There are other variations among the venoms of these snakes and in all cases the overall toxicity is a result of a synergistic characteristic between the different venom constituents. For instance of D. augusticeps the lethality of the whole venom is 5 to 15 times more toxic than its most lethal component.

Summary

Though the natural primary purpose of venom is primitive in nature, serving to secure prey and for defense, more clues to understanding its agents and reactions are more easily understood, when their subsequent purposes are contemplated. The first of these, which is relevant to securing of prey, is the immobilization of its prey. It is here where complex processes occur that prevent the ordinary physiological functions that maintain homeostasis. The velocity at which these agents reach the intended physiological targets and accomplish their purpose is a subject that evokes wonder. The processes and their results are comparable to a lock or switch, that when turned either prevents physiological processes by locking out  receptors or by unlocking and releasing agents that results in a malfunction. The individual toxins work together in a dynamic way to facilitate the processes and functions in the whole venom. Further investigation and understanding of these processes can provide a wealth of information about ordinary physiological processes and potential means of controlling them.

Barrett and Harvey  (1979) Effects of the Green Mamba. Br. J. Pharmacol 67:1. 99-105

Harris, J.B. (1991)Phospholipases in snake venoms and their effects on nerve and muscle Snake Toxins pp91-129 editor Harvey

Harvey and Anderson   (1991) Dendrotoxins: Snake Toxins       pp131-164 editor Harvey

Hider, Karlsson, Namiranian (1991) Snake Toxins pp1-34 editor Harvey

Kabara, J.J. and Fisher, G.H. Chemical compaosition of Naja naja venom Toxicon, 7 223 1969

Kornalik, F.   (1991) The influence of snake venom on coagulation Snake Toxinspp323-833 editor Harvey

Menez, Andre    (1991) Immunology of snake toxins Snake Toxins pp35-90 editor Harvey

Mobs, D. (1969) Preliminary studies on small molecular toxic components of elapid venoms Toxicon 6:247-253

Seegers and Ouyang (1979) Snake venoms and blood coagulation Snake venoms Handbook of experimental Pharmacology 52:684-750, Lee, C.Y. editor

Ownby, C.,  (1990) Locally acting agents Handbook of Toxinology, 601   Shier, W.T., Mebs, D. editors Marcel Dekker, New York

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