(1) Block of conduction and marked increase in permeability of the squid giant axon, when surrounded by adhering small nerve fibers, is caused by the venoms of cottonmouth, ringhals, and cobra snakes and by phospholipase A (PhA). This phenomenon is associated with a marked breakdown of the substructure of the Schwann sheath into masses of cytoplasmic globules. Low concentrations of these agents which render the axons sensitive to curare cause less marked changes in the structure of the sheath. (2) Rattlesnake venom, the direct lytic factor obtained from ringhals venom, and hyaluronidase caused few observable changes in structure, correlating with the inability of these agents to increase permeability. (3) Cottonmouth venom did not alter the structure of giant axons freed of all adhering small nerve fibers. This is in agreement with previous evidence that the venom effects are due to an action of lysophosphatides liberated as a result of PhA action. Cetyltrimethylammonium chloride, a cationic detergent, produces effects that resemble those of venom and PhA. (4) The results provide evidence that PhA is the component of the venoms that is responsible for their effects. It also appears that the Schwann cell and possibly the axonal membrane are the major permeability barriers in the squid giant axon.

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