Meldahl A S, Fonnum F
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller, Norway.
Toxicon. 1995 Aug;33(8):1071-86. doi: 10.1016/0041-0101(95)00038-n.
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 86Rb 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 microM) but not by the Ca2+ channel blockers omega-conotoxin GVIA (1 microM), diltiazem (100 microM), nifedipine (100 microM) or verapamil (100-500 microM). The increase in Na+ influx induced by the algal extract was insensitive to tetrodotoxin (3 microM) and procaine (100 microM), whereas both the Na+ influx and the membrane depolarization were inhibited by flunarizine (1-100 microM). The increase in K+ efflux was insensitive to flunarizine (5-100 microM). From these results it appears that the toxic extract of P. patelliferum 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.
已证明具有鱼毒性的海洋藻类扁藻（Prymnesium patelliferum）提取物对神经递质跨神经膜的转运有多种不同影响。它抑制L-谷氨酸和γ-氨基丁酸（GABA）的钠依赖性摄取，并增强乙酰胆碱的钙依赖性释放。因此，我们使用大鼠脑突触体研究了纯化的扁藻毒性提取物对一些膜特性的影响。我们发现，在藻类提取物抑制L-谷氨酸摄取的条件下，它增加了细胞内Na⁺和Ca²⁺的浓度，刺激了以⁸⁶Rb外流测定的K⁺外流，并使突触体膜去极化。对Na⁺/K⁺-ATP酶或哇巴因不敏感的ATP酶活性没有影响。此外，胞质标记乳酸脱氢酶（LDH）没有泄漏，这表明藻类提取物的各种作用并非由于突触体的非特异性泄漏或裂解。藻类提取物诱导的胞质游离Ca²⁺浓度升高依赖于细胞外Ca²⁺，并被氟桂利嗪（1 - 100微摩尔）抑制，但不被Ca²⁺通道阻滞剂ω-芋螺毒素GVIA（1微摩尔）、地尔硫䓬（100微摩尔）、硝苯地平（100微摩尔）或维拉帕米（100 - 500微摩尔）抑制。藻类提取物诱导的Na⁺内流增加对河豚毒素（3微摩尔）和普鲁卡因（100微摩尔）不敏感，而Na⁺内流和膜去极化均被氟桂利嗪（1 - 100微摩尔）抑制。K⁺外流增加对氟桂利嗪（5 - 100微摩尔）不敏感。从这些结果看来，扁藻的毒性提取物增加了突触体对Ca²⁺、Na⁺和K⁺的通透性，并且这些作用可能是质膜去极化和神经递质转运过程紊乱的原因。
