Calcium channel currents and their inhibition by (‐)‐baclofen in rat sensory neurones: modulation by guanine nucleotides.
Calcium channel currents and their inhibition by (‐)‐baclofen in rat sensory neurones: modulation by guanine nucleotides.
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大鼠感觉神经元中钙通道电流及其 (-)-巴氯芬的抑制：鸟嘌呤核苷酸的调节。
DOI：
10.1113/jphysiol.1987.sp016518
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
R. H. Scott
中科院分区：
文献类型：
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作者：
A. Dolphin;R. H. Scott
1. 在培养的大鼠背根神经节（d.r.g）神经元中，细胞内应用抗水解的GTP和GDP类似物，鸟苷5′‐O‐3‐硫代三磷酸（GTP‐γ‐S）和鸟苷5′‐O‐2‐硫代二磷酸（GDP‐β‐S）对电压激活的钙通道电流和γ -氨基丁酸B激动剂巴氯芬抑制它们的能力的影响进行了研究。2. 在控制条件下，使用全细胞贴片技术记录钙通道电流，以Ba2+而不是Ca2+作为渗透二价阳离子，由失活电流和持续电流组成。当膜片移液器中含有500 μ m - GTP - γ - S时，钙通道电流激活更慢，并且在100 ms去极化电压步骤中大部分不灭活。百日咳毒素预处理细胞可消除GTP - γ - S的作用。3. 与对照钙通道电流相比，在500微米- GDP - β - S存在下记录的钙通道电流具有更显著的瞬态成分。在无Na+介质中，当GDP - β - S存在时，瞬态钙通道电流的比例没有降低。4. GTP - γ - S和GDP - β - S对钙激活钾电流IK（Ca）、无Ca2+介质中激活的瞬态外向钾电流或超极化激活的内向整流电流（Ih）没有统计学上的显著影响。5. GTP - γ - S增加了巴氯芬抑制钙通道电流的能力，而GDP - β - S和百日咳毒素预处理细胞会降低这种能力。巴氯芬的半最大有效剂量（EC50）在GTP - γ - S存在时为2微米，对照组为15微米，在GTP - β - S存在时为50微米。使用单一浓度的腺苷激动剂2‐氯腺苷（2‐CA， 0.05微米）抑制钙通道电流也获得了类似的结果；GTP - γ - S显著增强了其作用，GDP - β - S显著降低了其作用。6. 巴氯芬抑制钙通道电流的能力不受1 μ m -福斯克林或50 μ m -细胞内环AMP的影响。由此得出结论，drg中的钙通道与核苷酸结合蛋白相关，这介导了巴氯芬和2 - CA对钙通道电流的影响。在没有激动剂的情况下，GTP - γ - S抑制钙通道电流瞬时组分的能力可能代表了一种差异调节钙通道活性的手段。
1. The effect of intracellular application of the hydrolysis‐resistant GTP and GDP analogues, guanosine 5'‐O‐3‐thiotriphosphate (GTP‐gamma‐S), and guanosine 5'‐O‐2‐thiodiphosphate (GDP‐beta‐S) has been examined on voltage‐activated calcium‐channel currents and the ability of the gamma‐aminobutyric acid B agonist baclofen to inhibit them, in cultured rat dorsal root ganglion (d.r.g.) neurones. 2. Under control conditions, the calcium‐channel current, recorded using the whole‐cell patch technique with Ba2+ rather than Ca2+ as the permeant divalent cation, consists of an inactivating and a sustained current. In the presence of 500 microM‐GTP‐gamma‐S included in the patch pipette, the calcium‐channel current was activated more slowly and was largely non‐inactivating during the 100 ms depolarization voltage step. The effects of GTP‐gamma‐S were abolished by pre‐treatment of cells with pertussis toxin. 3. The calcium‐channel current recorded in the presence of 500 microM‐GDP‐beta‐S had a more marked transient component than the control calcium‐channel current. The proportion of transient calcium‐channel current in the presence of GDP‐beta‐S was not reduced in Na+‐free medium. 4. No statistically significant effects of GTP‐gamma‐S and GDP‐beta‐S were observed on the calcium‐activated potassium current IK(Ca), the transient outward potassium current activated in Ca2+‐free medium, or on the inwardly rectifying current (Ih) activated by hyperpolarization. 5. GTP‐gamma‐S increased the ability of baclofen to inhibit calcium‐channel currents, whereas this was decreased by GDP‐beta‐S and by pre‐treatment of cells with pertussis toxin. The half‐maximal effective dose (EC50) for baclofen was 2 microM in the presence of GTP‐gamma‐S, 15 microM for control and 50 microM in the presence of GDP‐beta‐S. Comparable results were obtained using a single concentration of the adenosine agonist 2‐chloroadenosine (2‐CA, 0.05 microM) to inhibit calcium‐channel currents; its effect was significantly increased by GTP‐gamma‐S and reduced by GDP‐beta‐S. 6. The ability of baclofen to inhibit calcium‐channel currents was not affected by 1 microM‐forskolin or 50 microM‐intracellular cyclic AMP. 7. It is concluded that calcium channels in d.r.g.s are associated with a nucleotide binding protein, and that this mediates the effect of baclofen and 2‐CA on calcium‐channel currents. The ability of GTP‐gamma‐S to inhibit the transient component of calcium‐channel currents in the absence of agonist may represent a means of differentially regulating calcium‐channel activity.
腺苷酸环化酶和转导蛋白的调节成分。
DOI：
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发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Manning,DR;Gilman,AG
通讯作者：
Gilman,AG
β-肾上腺素能受体和视紫质与磷脂囊泡中重组的鸟嘌呤核苷酸调节蛋白功能相互作用的特异性。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Cerione,RA;Staniszewski,C;Benovic,JL;Lefkowitz,RJ;Caron,MG;Gierschik,P;Somers,R;Spiegel,AM;Codina,J;Birnbaumer,L
通讯作者：
Birnbaumer,L
百日咳毒素不抑制毒蕈碱受体介导的磷酸肌醇水解或钙动员。
DOI：
10.1042/bj2270933
发表时间：
1985
期刊：
The Biochemical journal
影响因子：
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作者：
Masters,SB;Martin,MW;Harden,TK;Brown,JH
通讯作者：
Brown,JH