氯通道阻滞剂对兔门静脉平滑肌细胞中钙激活氯电流和钾电流的影响。
Effects of Cl channel blockers on Ca-activated chloride and potassium currents in smooth muscle cells from rabbit portal vein.
作者信息
Hogg R C, Wang Q, Large W A
机构信息
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London.
出版信息
Br J Pharmacol. 1994 Apr;111(4):1333-41. doi: 10.1111/j.1476-5381.1994.tb14891.x.
Abstract
- The effects of some chloride channel antagonists were studied on the calcium-activated chloride current (ICl(Ca)) in smooth muscle cells from the rabbit portal vein with the perforated patch technique. 2. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and 4,4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (DIDS) reduced the amplitude of spontaneous transient inward currents (STICs, calcium-activated chloride currents) in a concentration-dependent manner. The concentrations required to reduce the amplitude by 50% (IC50) of STICs were 2.1 x 10(-4) M and 6.4 x 10(-4) M for DIDS and SITS, respectively. This effect was not voltage-dependent. 3. The time constant of decay of STICs (tau), which is voltage-dependent, was increased by about 30% by SITS and decreased by about 20% by DIDS. The effect of DIDS and SITS on tau was similar at holding potentials of -50 and +50 mV. 4. These compounds did not modify the characteristics of spontaneous transient outward currents (STOCs, calcium-activated potassium currents). 5. DIDS and SITS decreased the amplitude of ICl(Ca) evoked by noradrenaline and caffeine less potently than STICs with IC50 values of 7.5 x 10(-4) M and 1.8 x 10(-3) M, respectively. 6. DIDS and SITS increased the calcium-activated potassium current (IK(Ca) evoked by noradrenaline and caffeine by 3-6 fold. 7. Anthracene-9-carboxylic acid (A-9-C) inhibited STICs in a voltage-dependent fashion and was about 3 fold more active at +50 mV than at -50 mV. A-9-C increased STIC tau and this effect was enhanced by depolarization. 8. A-9-C also inhibited caffeine-evoked IC1(ca) but less potently than STICs and also increased the evoked IK(ca) without altering spontaneous IK(Ca).9. The results from the present work are compared with the pharmacology of other chloride conductances and the mechanism of action of the chloride channel antagonists in vascular smooth muscle is discussed.
摘要
- 采用穿孔膜片钳技术，研究了某些氯通道拮抗剂对兔门静脉平滑肌细胞钙激活氯电流（ICl(Ca)）的影响。2. 4-乙酰氨基-4'-异硫氰基芪-2,2'-二磺酸（SITS）和4,4'-二异硫氰基芪-2,2'-二磺酸（DIDS）以浓度依赖的方式降低了自发瞬时内向电流（STICs，钙激活氯电流）的幅度。使STICs幅度降低50%（IC50）所需的浓度，DIDS为2.1×10⁻⁴ M，SITS为6.4×10⁻⁴ M。这种效应不依赖电压。3. STICs的衰减时间常数（tau）依赖电压，SITS使其增加约30%，DIDS使其降低约20%。在-50和+50 mV的钳制电位下，DIDS和SITS对tau的影响相似。4. 这些化合物未改变自发瞬时外向电流（STOCs，钙激活钾电流）的特性。5. DIDS和SITS降低去甲肾上腺素和咖啡因诱发的ICl(Ca)幅度的作用比降低STICs的作用弱，IC50值分别为7.5×10⁻⁴ M和1.8×10⁻³ M。6. DIDS和SITS使去甲肾上腺素和咖啡因诱发的钙激活钾电流（IK(Ca)）增加3至6倍。7. 蒽-9-羧酸（A-9-C）以电压依赖的方式抑制STICs，在+50 mV时的活性比在-50 mV时高约3倍。A-9-C增加STIC的tau，去极化可增强这种效应。8. A-9-C也抑制咖啡因诱发的IC1(ca)，但作用比抑制STICs弱，并且增加诱发的IK(ca)，而不改变自发的IK(Ca)。9. 将本研究结果与其他氯电导的药理学进行了比较，并讨论了氯通道拮抗剂在血管平滑肌中的作用机制。
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本文引用的文献
1
Stilbenes stimulate T84 Cl- secretion by elevating Ca2+.芪类化合物通过升高钙离子水平刺激T84细胞的氯离子分泌。
Am J Physiol. 1993 Feb;264(2 Pt 1):G325-33. doi: 10.1152/ajpgi.1993.264.2.G325.
2
Effects of stilbenedisulfonic acid derivatives on the cAMP-regulated chloride current in cardiac myocytes.二苯乙烯二磺酸衍生物对心肌细胞中环磷酸腺苷调节的氯电流的影响。
Pflugers Arch. 1993 Feb;422(5):436-42. doi: 10.1007/BF00375068.
3
Chloride currents activated by caffeine in rat intestinal smooth muscle cells.咖啡因激活的大鼠肠道平滑肌细胞中的氯离子电流。
J Physiol. 1993 Jun;465:149-62. doi: 10.1113/jphysiol.1993.sp019670.
4
Time course of spontaneous calcium-activated chloride currents in smooth muscle cells from the rabbit portal vein.兔门静脉平滑肌细胞中自发性钙激活氯电流的时间进程。
J Physiol. 1993 May;464:15-31. doi: 10.1113/jphysiol.1993.sp019622.
5
Ca2+ and Ca(2+)-activated Cl- currents in rabbit oesophageal smooth muscle.兔食管平滑肌中的Ca2+和Ca(2+)激活的Cl-电流
J Physiol. 1993 Jan;460:117-33. doi: 10.1113/jphysiol.1993.sp019462.
6
Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina.对蝾螈视网膜单个视杆细胞内节中的电压激活电流和钙激活电流进行了研究。
J Physiol. 1982 Oct;331:253-84. doi: 10.1113/jphysiol.1982.sp014372.
7
A calcium-dependent transient outward current in Xenopus laevis oocytes.非洲爪蟾卵母细胞中的一种钙依赖性瞬时外向电流。
Proc R Soc Lond B Biol Sci. 1982 Jul 22;215(1201):491-7. doi: 10.1098/rspb.1982.0056.
8
Membrane mechanism associated with muscarinic receptor activation in single cells freshly dispersed from the rat anococcygeus muscle.从大鼠肛门尾骨肌新鲜分离的单细胞中与毒蕈碱受体激活相关的膜机制。
Br J Pharmacol. 1987 Oct;92(2):371-9. doi: 10.1111/j.1476-5381.1987.tb11333.x.
9
Calcium-activated chloride current in cultured sensory and parasympathetic quail neurones.培养的鹌鹑感觉神经元和副交感神经元中的钙激活氯电流
J Physiol. 1987 Dec;394:125-48. doi: 10.1113/jphysiol.1987.sp016863.
10
Autonomic regulation of a chloride current in heart.心脏中氯离子电流的自主调节。
Science. 1989 May 26;244(4907):983-5. doi: 10.1126/science.2543073.
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