ALPHA(1)-ADRENOCEPTORS IN RAT DORSAL RAPHE NEURONS - REGULATION OF 2 POTASSIUM CONDUCTANCES
ALPHA(1)-ADRENOCEPTORS IN RAT DORSAL RAPHE NEURONS - REGULATION OF 2 POTASSIUM CONDUCTANCES
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DOI：
10.1113/jphysiol.1994.sp020263
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发表时间：
1994-08-01
影响因子：
5.5
通讯作者：
WILLIAMS, JT
中科院分区：
文献类型：
--
作者：
PAN, ZZ;GRUDT, TJ;WILLIAMS, JT
1.α（1）-肾上腺素受体激活在大鼠中缝背核神经元中引起两种独立的效应：去极化和动作电位后超极化持续时间的增加。去极化常导致重复动作电位。α（1）肾上腺素受体拮抗剂哌唑嗪和WB 4101可阻断苯肾上腺素引起的去极化。WB 4101.2使苯丙氨酸浓度-反应曲线右移。在电压钳下，α 1肾上腺素受体激动剂在-60 mV引起内向电流，该电流在负电位下经常变小，但即使在强负电位下也很少反转极性。使用全细胞记录，在大多数细胞中，内向电流在钾的平衡电位处反转极性。胞内Cs+可减少或消除α 1介导的内向电流。内向电流依赖于外部钙，但不依赖于内部钙缓冲的程度。去除外部钙或加入MgCl 2、CoCl 2或CdCl 2，可降低或阻断α（1）-肾上腺素受体激动剂的作用。钡和锶支持甚至增强α 1-肾上腺素受体激动剂诱导的内向电流，而硝苯地平和ω-芋螺毒素则无此作用。相反，钙螯合剂1，2-双（O-氨基苯氧基）乙烷- N，N，N'N'-四乙酸（BAPTA）的内透析不抑制内向电流.通过在记录移液管中加入GTP-γ-S（100 μ M）来阻断（或封闭）α（1）诱导的去极化。4-佛波醇12，13-二丁酸酯（PDBu）对细胞膜电位无影响，但可抑制苯肾上腺素引起的去极化。这种抑制被非选择性蛋白激酶抑制剂staurosporin逆转。苯肾上腺素和去甲肾上腺素增加了一个单一的动作电位后超极化（晚AHP）的晚期成分。α（1）-敏感的晚期-AHP被阿帕明阻断，表明它是一种钙依赖性钾传导.毒胡萝卜素减少了晚期AHP的持续时间，并阻断了苯肾上腺素介导的延长。咖啡因也增强了晚期AHP，ryanodine阻断了咖啡因引起的增强。咖啡因不能阻断苯肾上腺素引起的增强作用，咖啡因引起的增强作用被ryanodine阻断后，苯肾上腺素引起的增强作用仍然存在.在预先用依那普利预处理的脑片中，α（1）-激动剂诱导的去极化没有改变;然而，晚期AHP的持续时间缩短，α（1）-受体介导的晚期AHP增强作用降低。结果表明，通过α（1）-肾上腺素受体激活中缝背核神经元的去极化是通过减少钾电导，这是独立的磷脂酶C途径的激活。晚期BHP的增加是通过从细胞内储存释放钙来介导的，并且可能在α（1）-肾上腺素受体激活诱导的去极化期间起到调节活性的作用。
1. alpha(1)-adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The alpha(1)-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101.2. Under voltage clamp, alpha(1)-adrenoceptor agonists caused an inward current at -60 m V, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the alpha(1)-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2, or CdCl2, reduced or blocked the effects of alpha(1)-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by alpha(1)-adrenoceptor agonists, whereas nifedipine and omega-conous toxin had no effect, In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane- N, N, N' N'-tetraacetic acid (BAPTA) did not inhibit the inward current.3. The alpha(1)-induced depolarization was blocked (or occluded) by the inclusion of GTP-gamma-S (100 mu M) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin.4. Phenylephrine and noradrenaline increased a late component of the afterhyperpolarization (late-AHP) that followed a single action potential. The alpha(1)-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance.5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine.6. In slices pretreated with manoalide the depolarization induced by alpha(1)-agonists was not changed; however, the late-AHP was reduced in duration and the alpha(1)-receptor-mediated augmentation of the late-AHP was decreased.7. The results suggest that the depolarization of dorsal raphe neurons by alpha(1)-adrenoceptor activation is through a decrease in potassium conductance that is independent of the activation of the phospholipase C pathway. The augmentation of the late-BHP is mediated by release of calcium from intracellular stores and may serve to regulate activity during the depolarization induced by alpha(1)-adrenoceptor activation.