Mechanism of phospholipase A2-induced conduction block in bullfrog sciatic nerve. I. Electrophysiology and morphology.
The effects of exogenously added phospholipase A2 (PLA2) and its hydrolytic products in isolated bullfrog sciatic nerve were investigated. Nerves were pretreated for 3 h with a dose of trypsin which did not affect conduction in order to enhance penetration of the added agents. Treatment of nerves with beta-glucosidase, neuraminidase or chymotrypsin had no effect on conduction. Whereas incubation of the nerves with normal Ringers for 2 h had no significant effect on conduction, incubation with PLA2 in Ringers caused decrements in the height of the compound action potential in a dose-related manner. In addition, incubation of the nerves with 10 mg/ml lysolecithin, arachidonic acid, or docosahexaenoic acid caused marked decrements in the height of the compound action potential. Electron microscopic analysis of nerves after each treatment which caused conduction block revealed varying levels of myelin damage. Although myelin was damaged at the paranodal and/or internodal region, depending on the agents used, the axonal membrane appeared to be intact at the ultrastructural level. It was concluded that the block in conduction resulting from PLA2 was due to the formation of lysolecithin and long chain polyunsaturated fatty acids.
D000818:Animals; D005227:Fatty Acids / Q000494:pharmacology; D008246:Lysophospholipids; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects; D009407:Nerve Block; D010525:Peripheral Nerves / Q000187:drug effects* / Q000648:ultrastructure; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000494:pharmacology; D011892:Rana catesbeiana; D012584:Sciatic Nerve / Q000187:drug effects
D005227:Fatty Acids; D008246:Lysophospholipids; D010743:Phospholipids; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2