THE EFFECTS OF A PURIFIED TOXIC EXTRACT OF PRYMNESIUM PATELLIFERUM ON TRANSPORT OF IONS THROUGH THE PLASMA MEMBRANE OF SYNAPTOSOMES

摘要

Extract of the ichthyotoxic marine alga Prymnesium patelliferum has been shown to have several different effects on the transport of neurotransmitters across nerve membranes, It inhibits the sodium dependent uptake of L-glutamate and GABA and enhances the calcium-dependent release of acetylcholine. We have therefore investigated the effects of a purified toxic extract of P. patelliferum on some membrane properties using rat brain synaptosomes. We found that under conditions where the algal extract inhibited the uptake of L-glutamate, it increased the intracellular concentrations of Na+ and Ca2+, stimulated efflux of K+ determined as Rb-86 efflux, and depolarized the synaptosomal membrane. There was no effect on Na+/K+-ATPase or ouabain-insensitive ATPase activities, Further, there was no leakage of the cytosolic marker LDH, indicating that the various effects of the algal extract were not due to nonspecific leakage or lysis of the synaptosomes. The rise in the cytosolic concentration of free Ca2+ induced by the algal extract was dependent on extracellular Ca2+, and was inhibited by flunarizine (1-100 mu M) but not by the Ca2+ channel blockers omega-conotoxin GVIA (1 mu M), diltiazem (100 mu M), nifedipine (100 mu M) or verapamil (100-500 mu M). The increase in Na+ influx induced by the algal extract was insensitive to tetrodotoxin (3 mu M) and procaine (100 mu M), whereas both the Na+ influx and the membrane depolarization were inhibited by flunarizine (1-100 mu M). The increase in K+ efflux was insensitive to flunarizine (5-100 mu M). From these results it appears that the toxic extract of P. patelliferum um increases the permeability of synaptosomes to Ca2+, Na+ and K+ and that these effects may be responsible for the plasma membrane depolarization and the disturbance of the neurotransmitter transport processes. [References: 47]