Voltage-gated Na+ channel (Nav channel) scorpion toxins are classified as α- and β-neurotoxins. Ts5 (α-neurotoxin) and Ts1 (β-neurotoxin) from Tityus serrulatus venom (TsV) interact with Nav channels, increasing N...Voltage-gated Na+ channel (Nav channel) scorpion toxins are classified as α- and β-neurotoxins. Ts5 (α-neurotoxin) and Ts1 (β-neurotoxin) from Tityus serrulatus venom (TsV) interact with Nav channels, increasing Na+ influx and activating voltage-dependent Ca2+ channels. This study aimed to investigate the effect of TsV, Ts1 and Ts5 on the cytosolic Ca2+ concentration ([Ca2+]C) in rat aortic smooth muscle cells. Toxins were isolated by ion exchange chromatography (Ts1) followed by RP-HPLC (Ts5). The rat aortic smooth muscle cells were isolated in Hanks buffer pH 7.4 and loaded with 5 μmol/L of Fura-2AM (45 minutes at 37℃), in order to measure [Ca2+]C by fluorescence of Fura-2/AM (ratio 340/380 nm). The fluorescence was measured in one single cell (excitation: 340 and 380 nm;emission: 510 nm). TsV (100 and 500 mg/mL) and its toxins Ts1 and Ts5 (50 and 100 mg/mL each) led to a concentration-dependent increase in [Ca2+]C. Tetrodotoxin (1 mmol/L), a Nav channel blocker, and verapamil (1 mmol/L), a voltage-operated Ca2+ channel blocker, inhibited the increase in [Ca2+]C induced by TsV (500 mg/mL). In conclusion, TsV and its toxins induce a concentration-dependent increase in [Ca2+]C that probably occurs through interaction with Nav channels, thus inducing depolarization and consequent Ca2+ influx. This assumption is based on the fact that this effect is inhibited by tetrodotoxin and verapamil, showing a direct action of TsV toxins on aorta smooth muscle cells.展开更多
The accurate knowledge of surgical anatomy,the amelioration of post-operative processes and the continuously increasing experience of surgeons nowadays allow the performance of severe hepatic operations(e.g.,wide live...The accurate knowledge of surgical anatomy,the amelioration of post-operative processes and the continuously increasing experience of surgeons nowadays allow the performance of severe hepatic operations(e.g.,wide liver resections,liver transplantations,etc.).The success of these operations is even more assisted by the great regenerative ability of the liver.Greek mythology,being an important source of information on the beliefs,habits,and phenomena observed during antiquity,reveals that hepatic regeneration was well known to ancient Greeks and this natural ability was established in two tales:the tale of Prometheus and the tale of the Giant Tityus.The main concept of both tales,being the destruction and reconstitution of the liver,is almost the same.Both of the condemned were immortal and their liver regenerated in a night,providing thus,food for the eagles and eternal pain for the sufferers.In conclusion,the tales show that the regenerative ability of the liver was well known from early years and that the trust shown by the Gods in this ability,to cause eternal suffering is on a par with the trust shown by the modern surgeons in it,to assure a successful hepatic operation.展开更多
基金supported by grants from Fundacao de Amparoa Pesquisa do Estado de Sao Paulo(FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq).
文摘Voltage-gated Na+ channel (Nav channel) scorpion toxins are classified as α- and β-neurotoxins. Ts5 (α-neurotoxin) and Ts1 (β-neurotoxin) from Tityus serrulatus venom (TsV) interact with Nav channels, increasing Na+ influx and activating voltage-dependent Ca2+ channels. This study aimed to investigate the effect of TsV, Ts1 and Ts5 on the cytosolic Ca2+ concentration ([Ca2+]C) in rat aortic smooth muscle cells. Toxins were isolated by ion exchange chromatography (Ts1) followed by RP-HPLC (Ts5). The rat aortic smooth muscle cells were isolated in Hanks buffer pH 7.4 and loaded with 5 μmol/L of Fura-2AM (45 minutes at 37℃), in order to measure [Ca2+]C by fluorescence of Fura-2/AM (ratio 340/380 nm). The fluorescence was measured in one single cell (excitation: 340 and 380 nm;emission: 510 nm). TsV (100 and 500 mg/mL) and its toxins Ts1 and Ts5 (50 and 100 mg/mL each) led to a concentration-dependent increase in [Ca2+]C. Tetrodotoxin (1 mmol/L), a Nav channel blocker, and verapamil (1 mmol/L), a voltage-operated Ca2+ channel blocker, inhibited the increase in [Ca2+]C induced by TsV (500 mg/mL). In conclusion, TsV and its toxins induce a concentration-dependent increase in [Ca2+]C that probably occurs through interaction with Nav channels, thus inducing depolarization and consequent Ca2+ influx. This assumption is based on the fact that this effect is inhibited by tetrodotoxin and verapamil, showing a direct action of TsV toxins on aorta smooth muscle cells.
文摘The accurate knowledge of surgical anatomy,the amelioration of post-operative processes and the continuously increasing experience of surgeons nowadays allow the performance of severe hepatic operations(e.g.,wide liver resections,liver transplantations,etc.).The success of these operations is even more assisted by the great regenerative ability of the liver.Greek mythology,being an important source of information on the beliefs,habits,and phenomena observed during antiquity,reveals that hepatic regeneration was well known to ancient Greeks and this natural ability was established in two tales:the tale of Prometheus and the tale of the Giant Tityus.The main concept of both tales,being the destruction and reconstitution of the liver,is almost the same.Both of the condemned were immortal and their liver regenerated in a night,providing thus,food for the eagles and eternal pain for the sufferers.In conclusion,the tales show that the regenerative ability of the liver was well known from early years and that the trust shown by the Gods in this ability,to cause eternal suffering is on a par with the trust shown by the modern surgeons in it,to assure a successful hepatic operation.
