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智利狼蛛(Phrixotrichus spatulatus)毒液对豚鼠离体心室肌细胞的作用。

The effect of the venom of a Chilean tarantula, Phrixotrichus spatulatus, on isolated guinea pig ventricular myocytes.

作者信息

Pascarel C, Cazorla O, Le Guennec J Y, Orchard C H, White E

机构信息

Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, CNRS, UMR 6542, Faculté des Sciences, Tours, France.

出版信息

Toxicol Appl Pharmacol. 1997 Dec;147(2):363-71. doi: 10.1006/taap.1997.8291.

Abstract

We have investigated the effect of the venom of a Chilean tarantula, Phrixotrichus spatulatus, on cell contraction, intracellular [Ca2+] ([Ca2+]i), and the L-type Ca2+ current (ICa,L) in cells isolated from the ventricles of guinea pig hearts. Whole-cell voltage clamp techniques were used to monitor ICa,L. The action potential was recorded using whole cell current clamp. [Ca2+]i was monitored using the fluorescent indicator indo-1. The venom of P. spatulatus decreased ICa,L in a dilution-dependent manner, with half-maximal inhibition at a dilution of 1.1/10(4) (v/v). At a dilution of 1/10(4), this inhibition occurred at all potentials so that the current-voltage relationship of ICa,L was depressed. However, inhibition of ICa,L by the venom was relieved by positive potentials, the venom being less effective following pulses to positive potentials. The venom reduced the duration of the action potential (at 50% repolarization) by between 26 and 43%. The venom also decreased the amplitude of the [Ca2+]i transient and cell contraction. It is concluded that the venom of P. spatulatus is a potent, voltage-dependent inhibitor of ICa,L; this inhibition of ICa,L may account for the effects of the venom on action potential duration, [Ca2+]i, and contraction.

摘要

我们研究了智利狼蛛(Phrixotrichus spatulatus)毒液对从豚鼠心室分离的细胞的收缩、细胞内[Ca2+]([Ca2+]i)以及L型Ca2+电流(ICa,L)的影响。采用全细胞电压钳技术监测ICa,L。使用全细胞电流钳记录动作电位。使用荧光指示剂indo-1监测[Ca2+]i。P. spatulatus毒液以稀释依赖的方式降低ICa,L,在1.1/10(4)(v/v)的稀释度下达到半数最大抑制。在1/10(4)的稀释度下,这种抑制在所有电位下均会发生,使得ICa,L的电流-电压关系降低。然而,毒液对ICa,L的抑制可被正电位解除,在施加正电位脉冲后毒液的作用减弱。毒液使动作电位持续时间(复极化50%时)缩短了26%至43%。毒液还降低了[Ca2+]i瞬变的幅度和细胞收缩。结论是,P. spatulatus毒液是一种强效的、电压依赖性的ICa,L抑制剂;对ICa,L的这种抑制可能解释了毒液对动作电位持续时间、[Ca2+]i和收缩的影响。

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