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脊椎动物视杆细胞中环鸟苷酸门控电导的拮抗剂可阻断扇贝纤毛光感受器中的光电流。

Antagonists of the cGMP-gated conductance of vertebrate rods block the photocurrent in scallop ciliary photoreceptors.

作者信息

Gomez M P, Nasi E

机构信息

Department of Physiology, Boston University School of Medicine, MA 02118, USA.

出版信息

J Physiol. 1997 Apr 15;500 ( Pt 2)(Pt 2):367-78. doi: 10.1113/jphysiol.1997.sp022027.

Abstract
  1. Hyperpolarizing scallop photoreceptors, like vertebrate rods, use cGMP as an internal messenger and their light-sensing structure is also of ciliary origin. To ascertain possible functional similarities between the light-sensitive conductances in the two classes of visual cells, we examined in scallop photoreceptors the effects of several antagonists of the photocurrent of rods. 2. Extracellular application of L-cis-diltiazem rapidly and reversibly suppressed the photocurrent. The effect was stereospecific and dose dependent, with a K1/2 of approximately 400 microM. Intracellular dialysis at lower doses (100-200 microM) also induced a substantial inhibition. 3. L-cis-Diltiazem reduced the light-activated conductance without shifting the intensity-response curve. Furthermore, the drug also blocked the current directly evoked by application of cGMP. These observations indicate that the inhibitory effects result from blockage of the conductance, rather than from impairment of the activating cascade. 4. The fractional blockage increased e-fold per approximately 55 mV depolarization, regardless of the side of drug application, as if the charged form of L-cis-diltiazem can only access the blocking site from the intracellular compartment. 5. The amiloride derivative 3',4'-dichlorobenzamil potently suppressed the photocurrent (K1/2 approximately 5 microM), without affecting its kinetics or operating range. Amiloride itself was also effective at higher concentrations. 6. The pharmacological resemblance of these light-dependent channels to those of rods and cones indicates that significant aspects of the transduction cascade are conserved across disparate sensory cells of ciliary origin.
摘要
  1. 超极化的扇贝光感受器与脊椎动物的视杆细胞一样,将环鸟苷酸(cGMP)用作内部信使,并且它们的光感测结构也起源于纤毛。为了确定这两类视觉细胞中光敏感电导之间可能存在的功能相似性,我们在扇贝光感受器中研究了几种视杆细胞光电流拮抗剂的作用。2. 细胞外应用L-顺式地尔硫卓可快速且可逆地抑制光电流。该效应具有立体特异性且呈剂量依赖性,半数抑制浓度(K1/2)约为400微摩尔。较低剂量(100 - 200微摩尔)的细胞内透析也会引起显著抑制。3. L-顺式地尔硫卓降低了光激活的电导,而不改变强度-反应曲线。此外,该药物还阻断了由应用cGMP直接诱发的电流。这些观察结果表明,抑制作用是由于电导的阻断,而非激活级联反应的受损。4. 无论药物应用的一侧如何,每约55毫伏去极化,分数阻断增加e倍,就好像L-顺式地尔硫卓的带电形式只能从细胞内区室进入阻断位点。5. 氨氯地平衍生物3',4'-二氯苯甲酰胺可有效抑制光电流(K1/2约为5微摩尔),而不影响其动力学或作用范围。氨氯地平本身在较高浓度时也有效。6. 这些光依赖性通道与视杆细胞和视锥细胞通道的药理学相似性表明,转导级联反应的重要方面在不同的纤毛起源感觉细胞中是保守的。

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