Mechanism of phospholipase A2-induced conduction block in bullfrog sciatic nerve. II. Biochemistry.
The biochemical changes associated with conduction block following exogenous application of purified phospholipase A2 to bullfrog sciatic nerves were investigated. Nerves were treated with concentrations of phospholipase A2 needed to produce at least a 50% decrease in the compound action potential after a 2-2 1/2 h incubation. This phospholipase A2-induced conduction block was associated with lipid hydrolysis, depletion of high energy phosphates and decreases in [3H]saxitoxin binding. Forty-two percent of the nerve phosphatidylcholine and 45% of the nerve phosphatidylethanolamine were hydrolyzed. [3H]Saxitoxin binding was decreased by 85% in association with conduction block attained with phospholipase A2 incubation. There were significant decrements in adenosine triphosphate levels (-58%) and in phosphocreatine levels (-78%), but no difference in the specific activities of these phosphate compounds. It is concluded that a number of mechanisms can account for the conduction failure resulting from phospholipase A2, including disruption of sodium channels needed for propagation of regenerative nerve impulses and the depletion of high energy phosphates needed to maintain ionic gradients.
D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D009407:Nerve Block; D010525:Peripheral Nerves / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000032:analysis; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000032:analysis; D011892:Rana catesbeiana
D000227:Adenine Nucleotides; D010710:Phosphates; D010743:Phospholipids; D010725:Phosphocreatine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2