VARIATION IN SEROTONERGIC INHIBITION OF CALCIUM-CHANNEL CURRENTS IN 4 TYPES OF RAT SENSORY NEURONS DIFFERENTIATED BY MEMBRANE-PROPERTIES
VARIATION IN SEROTONERGIC INHIBITION OF CALCIUM-CHANNEL CURRENTS IN 4 TYPES OF RAT SENSORY NEURONS DIFFERENTIATED BY MEMBRANE-PROPERTIES
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DOI：
10.1152/jn.1995.74.5.1870
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发表时间：
1995-11-01
影响因子：
2.5
通讯作者：
SCROGGS, RS
中科院分区：
文献类型：
--
作者：
CARDENAS, CG;DELMAR, LP;SCROGGS, RS
1.根据动作电位（AP）时程、辣椒素敏感性、I-H、I-A和N-、L-和T-型钙通道电流的表达筛选大鼠背根神经节（DRG）细胞体。在-60 mV的膜电位下，在总振幅的一半处测量AP持续时间。对辣椒素的敏感性定义为1 μ M辣椒素在-60 mV的保持电位（HP）下产生内向电流。通过从-60 mV的HP到-110 mV的787-ms超极化诱发I-H。在787-ms超极化至-110 mV后，通过复极化至-60 mV诱发I-A。高阈值Ca 2+通道电流通过从-60 mV的HP去极化至-10或0 mV来诱发，并且使用选择性Ca 2+通道阻断剂（尼莫地平和ω-芋螺毒素GVIA）来分级L-和N-型Ca 2+通道电流。T-型Ca 2+通道电流通过从-90 mV的HP去极化至-40 mV来诱发。研究的116个DRG细胞中有97个根据上述特征的表达密切符合四种类别之一。这四个类别（称为类型1-4）如下所述。2. 1型DRG细胞（索马直径24.6 +/- 0.5 μ m，平均值+/- SE; n = 34）具有长持续时间的AP（平均值= 9.8 ms），在跌倒肢体上具有突出的肩部，并且对辣椒素敏感。不表达显著的I-H或I-A。高阈值Ca 2+通道电流平均为28% ω-芋螺毒素GVIA敏感（N型）和46%尼莫地平敏感（L型）; 26%对两种阻断剂均具有抗性（抗性）。T型Ca 2+通道电流平均为245 pA.3。2型DRG细胞（索马直径25.2 +/- 0.9 μ m，n = 19）具有短持续时间的AP（平均= 2.9 ms），在下降肢体上具有小肩，并且对辣椒素敏感。I-H可忽略不计，但I-A平均为184 pA。高阈值Ca 2+通道电流平均为42%的N型，23%的L型，和35%的电阻。T型Ca 2+通道电流平均为47 pA.4。3型DRG细胞（索马直径18.6 +/- 0.8 μ m，n = 21）具有短持续时间的AP（平均= 1.8 ms），并且对辣椒素不敏感。I-A不表达，但I-H平均为147 pA。高阈值Ca 2+通道电流平均为27%的N型，44%的L型，和29%的电阻。T型Ca 2+通道电流平均为306 pA。4型DRG细胞（索马直径33.9 +/- 0.4 μ m，n = 23）具有短持续时间的AP（平均= 1.1 ms），并且对辣椒素不敏感。I-A不表达，但I-H平均为810 pA。高阈值Ca ~（2+）通道电流N型占16%，L型占4%，阻力型占80%。T型Ca 2+通道电流平均为4，031 pA.6。5-羟色胺（5-HT）和（+）8-OH-DPAT在1型DRG细胞与2-4型DRG细胞中对高阈值Ca 2+通道电流的抑制有很大的变化。平均而言，5-HT（10 μ M）抑制高阈值钙通道电流的平均42%，在1型DRG细胞，与15%，18%，和7%的抑制2-4型，分别。类似地，（+）8-OH-DPAT（1 μ M）在1型DRG细胞中平均抑制高阈值Ca 2+通道电流35%，而在2-4型DRG细胞中分别抑制5%、8%和3%。这是可能的，DRG细胞的膜特性的表达不同，可能代表感觉神经元，传递不同类型的感觉信息。因此，5-HT和（+）8-OH-DPAT对上述几类DRG细胞Ca ~（2+）通道电流抑制的差异可能表明，5-HT_（1A）受体激活对某些类型DRG感觉神经元Ca ~（2+）内流的抑制作用比其他类型的更强。
1. Rat dorsal root ganglion (DRG) cell bodies were screened according to action potential (AP) duration, capsaicin sensitivity, expression of I-H, I-A, and N-, L-, and T-type Ca2+ channel currents. AP duration was measured at half of total amplitude at a membrane potential of -60 mV. Sensitivity to capsaicin was defined as production of an inward current at a holding potential (HP) of -60 mV by 1 mu M capsaicin. I-H was evoked by a 787-ms hyperpolarization to -110 mV from an HP of -60 mV. I-A was evoked by repolarization to -60 mV after a 787-ms hyperpolarization to -110 mV. High-threshold Ca2+ channel current was evoked by a depolarization to -10 or 0 mV from an HP of -60 mV, and L- and N-type Ca2+ channel current was fractionated using selective Ca2+ channel blockers (nimodipine and omega-conotoxin GVIA). T-type Ca2+ channel current was evoked by a depolarization to -40 mV from an HP of -90 mV. Ninety-seven of the 116 DRG cells studied fit closely into one of four categories based on expression of the above characteristics. These four categories, referred to as types 1-4, are described below.2. Type 1 DRG cells (soma diameter 24.6 +/- 0.5 mu m, mean +/- SE; n = 34) had long-duration APs (average = 9.8 ms) with a prominent shoulder on the falling limb and were capsaicin sensitive. Significant I-H or I-A was not expressed. High-threshold Ca2+ channel current was on average 28% omega-conotoxin GVIA sensitive (N-type) and 46% nimodipine sensitive (L-type); 26% was resistant to both blockers (resistant). T-type Ca2+ channel currents averaged 245 pA.3. Type 2 DRG cells (soma diameter 25.2 +/- 0.9 mu m, n = 19) had short-duration APs (average = 2.9 ms) with a small shoulder on the falling limb and were capsaicin sensitive. I-H was negligible but I-A averaged 184 pA. High-threshold Ca2+ channel current averaged 42% N-type, 23% L-type, and 35% resistant. T-type Ca2+ channel currents averaged 47 pA.4. Type 3 DRG cells (soma diameter 18.6 +/- 0.8 mu m, n = 21) had short-duration APs (average = 1.8 ms) and were insensitive to capsaicin. I-A was not expressed but I-H averaged 147 pA. High-threshold Ca2+ channel current averaged 27% N-type, 44% L-type, and 29% resistant. T-type Ca2+ channel currents averaged 306 pA.5. Type 4 DRG cells (soma diameter 33.9 +/- 0.4 mu m, n = 23) had short-duration APs (average = 1.1 ms) and were capsaicin insensitive. I-A was not expressed but I-H averaged 810 pA. High-threshold Ca2+ channel current was 16% N-type, 4% L-type, and 80% resistant. T-type Ca2+ channel currents averaged 4,031 pA.6. There was a large variation in the inhibition of high-threshold Ca2+ channel currents by serotonin (5-HT) and (+)8-OH-DPAT in type 1 DRG cells versus types 2-4. On average, 5-HT (10 mu M) inhibited high-threshold Ca2+ channel current by an average of 42% in type 1 DRG cells, compared with 15%, 18%, and 7% inhibition in types 2-4, respectively. Similarly, (+)8-OH-DPAT (1 mu M) inhibited high-threshold Ca2+ channel current by an average of 35% in type 1 DRG cells, compared with 5%, 8%, and 3% inhibition in types 2-4, respectively.7. It is possible that DRG cells that vary in their expression of membrane properties may represent sensory neurons that transmit different types of sensory information. Thus the variation in inhibition of Ca2+ channel current by 5-HT and (+)8-OH-DPAT in the above categories of DRG cells may indicate that 5-HT1A receptor activation inhibits Ca2+ entry into some types of DRG sensory neurons more than others.