Biomaterial Database

Comparative effects of phospholipase A2 neurotoxins and enzymes on membrane potential and Na+/K+ ATPase activity in rat brain synaptosomes. 1991

S L Yates, and P Rosenberg

Section of Pharmacology and Toxicology, University of Connecticut, School of Pharmacy Storrs 06269.

Beta-Bungarotoxin (beta-BuTX) and notexin are phospholipase A2 (PLA2) neurotoxins which cause an irreversible blockade of neurotransmitter release through specific and potent effects at the presynaptic nerve terminal; however, their mechanism of action is uncertain. We examined the effects of beta-BuTX and notexin on Na+/K+ ATPase activity using Sprague-Dawley rat brain synaptosomes in order to determine if alterations in activity might modulate neurotoxin-induced depolarization. Treatment of synaptosomes with 0.05 to 5 nM beta-BuTX, notexin, and Naja naja atra and Naja nigricollis PLA2 (PLA2 enzymes without selective presynaptic actions) caused a dose-dependent depolarization of synaptosomes with no differences being observed between the effects of the PLA2 neurotoxins and enzymes. N. nigricollis PLA2 (0.5 nM; 20 min) slightly stimulated Na+/K+ ATPase activity while beta-BuTX and notexin (0.5 nM: 10 and 20 min) were without effect. With 50 nM concentrations beta-BuTX and notexin stimulated Na+/K+ ATPase activity, while N. nigricollis and N. n. atra PLA2 inhibited activity. The effects on membrane potential and Na+/K+ ATPase were antagonized or blocked by EDTA (10 mM) and bovine serum albumin (1 mg/ml), suggesting that PLA2 enzymatic activity is essential for their effects on membrane potential and Na+/K+ ATPase activity. Following neurotoxin and enzyme pretreatment, we found a biphasic correlation between synaptosomal free fatty acid (FFA) levels and Na+/K+ ATPase activity, where Na+/K+ ATPase is stimulated by low levels of FFA (0.13 to 0.22 mumol/mg protein) and antagonized by FFA levels in excess of 0.34 mumol/mg protein. In contrast there was a linear correlation between the extent of FFA production and membrane depolarization. We propose that the presynaptic depolarizing actions of beta-BuTX and notexin are not mediated through modulation of Na+/K+ ATPase activity and that the changes observed in ATPase activity and possibly membrane potential are directly due to PLA2 enzymatic activity and the production of FFA.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009498	Neurotoxins	Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.	Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D010741	Phospholipases A	Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002038	Bungarotoxins	Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.	alpha-Bungarotoxin,beta-Bungarotoxin,kappa-Bungarotoxin,alpha Bungarotoxin,beta Bungarotoxin,kappa Bungarotoxin
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004546	Elapid Venoms	Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.	Cobra Venoms,Elapidae Venom,Elapidae Venoms,Naja Venoms,Cobra Venom,Elapid Venom,Hydrophid Venom,Hydrophid Venoms,King Cobra Venom,Naja Venom,Ophiophagus hannah Venom,Sea Snake Venom,Sea Snake Venoms,Venom, Cobra,Venom, Elapid,Venom, Elapidae,Venom, Hydrophid,Venom, King Cobra,Venom, Naja,Venom, Ophiophagus hannah,Venom, Sea Snake,Venoms, Cobra,Venoms, Elapid,Venoms, Elapidae,Venoms, Hydrophid,Venoms, Naja,Venoms, Sea Snake
D005230	Fatty Acids, Nonesterified	FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.	Fatty Acids, Free,Free Fatty Acid,Free Fatty Acids,NEFA,Acid, Free Fatty,Acids, Free Fatty,Acids, Nonesterified Fatty,Fatty Acid, Free,Nonesterified Fatty Acids