原裸甲藻毒素對牛腎上腺嗜鉻細胞的影響

Abstract

原裸甲藻毒素(Brevetoxin, PbTxs)為紅潮發生時藻類所產出的神經毒素之一，並根據其結構分為兩種類別：原裸甲藻毒素A型(Brevetoxin-A)及原裸甲藻毒素B型(Brevetoxin -B)。目前已知會與電壓調控型鈉離子通道第五結合位結合，並改變通道門閥之開啟機制。過去在細胞電生理方面，除了以螯蝦及烏賊之巨大神經為研究題材外，對於哺乳類動物細胞電生理特性的影響，以及在胞吐作用以及胞吞作用上是否造成改變，卻甚少有文獻探討。本研究以牛腎上腺嗜鉻細胞為題材，其屬於神經內分泌細胞，藉由探討原裸甲藻毒對嗜鉻細胞電生理特性的影響，以了解毒素對神經細胞可能之作用。以全細胞膜片箝制觀察嗜鉻細胞之鈉離子通道電生理特性，結果發現原裸甲藻毒素A型中的PbTx-1在1uM濃度下會抑制牛腎上腺嗜鉻細胞鈉離子電流，並使恆穩態不活化曲線之曲線中點自-43.1±2.2 mV左移至-58.3±3.5 mV。原裸甲藻毒素對嗜鉻細胞鈉離子通道的調控，顯示其對嗜鉻細胞動作電位的釋放、胞吐與胞吞作用的影響可能性之存在，生理上之作用機制值得我們進一步探討。

Brevetoxins (PbTx) are the major neurotoxin produced by algae when red tide happens and are classified according to their chemical structure named Brevetoxin-A(PbTx-A) and Brevetoxin-B(PbTx-B). Researches in the past believe that these toxins bind to Na+ channel and affect its activation and inactivation. Reports in the past focused on the classification, purification and detection of the toxin. For the electrophysiology study, crafish and squid giant axon were used as model systems. Yet few people used neuroendocrine cells as the model system to study the effect of the toxin to Na+ channel modulation, exocytose secretion and firing of action potential. In this report we use bovine adrenal chromaffin cells to test whether its electrophysiological feature will change after toxin treatment. Our results showed that 1 uM of PbTx-1, one kind of PbTx-A, shifted the inactivaion and decreased the conductance of Na+ channel in bovine chromaffin cells. These results indicate that PbTx may modulate the action potential firing, exocytosis and endocytosis in neuroendocrine cells.