石杉碱甲增强大鼠海马脑片CA1锥体神经元的兴奋性突触传递

目的:观察石杉碱甲(Hup-A)对海马CA1锥体神经元兴奋性突触传递的影响,以探讨其增强学习记忆功能的神经细胞电生理机制。方法:应用大鼠海马脑片CA1锥体神经元细胞内记录技术,观察Hup-A对大鼠海马CA1锥体神经元膜电性质和刺激Schaffer侧支诱发的兴奋性突触后电位(EPSP)的影响。结果:(1)Hup-A(1μmol/L)灌流15min对CA1锥体神经元的膜电性质没有显著性影响。(2)Hup-A(0.3～3.0μmol/L)浓度依赖性使EPSP幅度升高、时程延长、曲线下面积增大,该作用可被阿托品(10μmol/L)预处理取消。(3)Hup-A对外源性谷氨酸诱导的去极化反应无明显影响。结论:Hup-A可增强CA1锥体神经元的兴奋性突触传递,其增强突触传递作用与M型乙酰胆碱受体激动有关。     

9-氨基四氢吖啶对颈上神经节胆碱能传递的增强和抑制作用

用大鼠颈上神经节细胞内记录技术对9-氨基四氢吖啶(THA)的作用进行了观察,发现低浓度(0·l或1μmol·L~(-1))灌流可增强快兴奋性突触后电位(f-EPSP,n=26)及外源性A Ch电位(n=19),但高浓度(50 或100μmol·L~(-1))不仅抑制f-EPSP(n=17)和ACh电位(n=4),且抑制氨甲酰胆碱电位(n=5)。结果表明THA因抗胆碱酯酶而增强胆碱能传递,但高浓度能抑制其传递。     

Adrenoceptor agonists inhibit calcium-dependent potentials in rat stelate ganglion neurons

探索肾上腺素能受体激动剂对大鼠星状神经节细胞的作用及其作用机制．方法：离体交感神经节细胞内生物电记录．结果：去甲肾上腺素，可乐定（１０－３０μｍｏｌ·Ｌ－１）可逆地抑制细胞动作电位；依钙后超极化电位；在含ＴＴＸ与ＴＥＡ克氏液中记录到的钙锋电位及快兴奋性突触后电位．结论：肾上腺素受体激动剂对三种钙电位及快兴奋性突触后电位的抑制作用可能是其在突触前膜对钙内流的抑制所致．     

9—氨基四氢吖啶对上神经节胆碱能传递的增强的抑制作用

用大鼠颈上神经节细胞内记录技术对９－氨基四氢吖啶（ＴＨＡ）的作用进行了观察，发现低浓度（０．１或１μｍｏｌ．Ｌ－１）灌流可增强快兴奋性突触后位（ｆ－ＥＰＳＰ，ｎ＝２６）及外源性ＡＣｈ电位（ｎ＝１９），但高浓度（５０或１００μｍｏｌ．Ｌ－１）不仅抑制ｆ－ＥＰＳＰ（ｎ＝１７）和ＡＣｈ电位（ｎ＝４），且抑制氨甲酰胆碱电位（ｎ＝５）。结果表明ＴＨＡ抗胆碱酯酶而增强胆碱能传递，但高浓度能抑制其传递。     

在不均匀牵张大鼠膈肌标本上新霉素对接头作用的进一步研究

在不均匀牵张的大鼠离体膈肌标本上,同时记录同一终板的小终板电位(MEPP),终板电位(EPP)和微电泳外源性乙酰胆碱(ACh)诱发的乙酰胆碱电位(AChP)。以AChP幅度为突触后膜兴奋性大小指标,对MEPP和EPP进行校正;以量子含量M和二项统计参数即刻可释放量子贮存n及平均量子释放机率P为突触前递质释放指标,定量观察了新霉素(neomycin)对突触前和突触后的作用。结果表明新霉素(30μmol/L,100μmol/L)作用20min,对AChP,MEPP无影响,M_l,M_x,n和P明显下降,串EPPs(50Hz)出现脱落现象,表明此浓度下的新霉素对接头的作用主要是抑制突触前诱发的递质释放,对自发释放的量子大小并无影响。其机理可能是新霉素拮抗Ca~(2+)内流,减小n和P,从而降低诱发的递质释放。     

三七总皂苷抗大鼠心肌肥大的作用及其神经机制

目的　探讨三七总皂苷 (PNS)抗腹主动脉缩窄大鼠压力超负荷性心肌肥大的神经机制。方法　①用腹主动脉缩窄法建立心肌肥大模型 ,将大鼠分为假手术对照组、腹主动脉缩窄组及低、中、高剂量组 ,3个剂量组分别每日腹腔注射5 0、10 0和 15 0mgPNS·kg-1。 3wk后处死大鼠检测全心重量/体重 (HW/BW )、左室重量指数 (LVI) ,左心室组织切片HE染色后测心肌纤维直径 (MD)。②细胞内生物电记录技术观察PNS对大鼠星状神经节 (SG)的快兴奋性突触后电位 (f EPSP)、膜电位、膜电阻及对外源性乙酰胆碱引起的膜除极化反应的影响。结果　①高剂量组的HW /BW、LVI及MD显著低于缩窄组 ,P <0 0 1;中剂量组与缩窄组比较MD显著降低 ,P <0 0 5 ;低剂量组与缩窄组比较 ,HW/BW ,LVI和MD三项指标均无显著的变化。②PNS在 0 10～ 0 16g·L-1浓度范围内可使大鼠星状神经节f EPSP可逆性减小 ,PNS还可拮抗高钙对f EPSP的易化作用 ,但对膜电位、膜电阻及外源性ACh引起的膜除极反应无显著的影响。结论　PNS对f EPSP的抑制可能是其抗压力超负荷性心肌肥大的神经机制 ,而抑制作用则是通过突触前机制产生 ,且与拮抗Ca2 + 内流有关。     

匹诺塞林对体外共培养海兔SN/L7神经元电生理活动的作用

目的研究匹诺塞林(PNCB)对海兔神经元共培养体系(SN/L7)的电生理效应,探讨可能的作用机制。方法体外共培养海兔(aplysia)的感觉神经元(SN)和运动神经元(L7),使其互相接触形成突触连接。细胞培养至d 5,给予不同浓度的PNCB刺激,考察药物对SN/L7兴奋性突触后电位(EPSP)的影响,随后撤去药物,观察EPSP的恢复情况。另取细胞,在PNCB孵育后加入0.005 mmol.L-15-羟色胺(5-HT),观察SN/L7对5-HT的反应性的变化。结果 PNCB作用5 min,使SN/L7的EPSP幅值降低。药物浓度低于0.1 mmol.L-1时,作用强度与药物剂量呈负线性关系(r>0.995),在0.1～0.4 mmol.L-1的浓度范围内,作用强度与药物剂量呈正线性关系(r>0.998);撤去药物后,SN/L7的EPSP幅值可恢复至初始值。PNCB使SN/L7对5-HT的反应性消失,撤去药物后,该反应性得以恢复。结论 PNCB可逆地抑制体外共培养的海兔SN/L7神经元突触的兴奋性传导,并可逆地抑制SN/L7对5-HT的反应性。这一效应可能与突触后膜的谷氨酸受体有关。     

氯化镧对兔颈上交感神经节突触传递的影响

以蔗糖间隙法观察镧（Ｌａ３＋）对离体兔颈上交感神经节突触传递的影响。由顺向刺激诱发的复合神经节动作电位（ＡＰｃ），Ｎ电位（相当于快兴奋性突触后电位），以及后超极化和Ｐ电位（相当于慢抑制性突触后电位），被用作突触反应的指标。在浓度为２０，４０，８０和１６０μｍｏｌ·Ｌ－１时，ＬａＣｌ３减小ＡＰｃ和Ｎ波的幅度，而以ＬａＣｌ３灌流后，对节前神经干的动作电位并无明显影响。后超极化及Ｐ电位先有增大，继而也被抑制。ＬａＣｌ３（４０μｍｏｌ·Ｌ－１）可减弱无钙Ｋｒｅｂｓ液对ＡＰｃ的抑制效应。高钙（１０ｍｍｏｌ·Ｌ－１）则可拮抗ＬａＣｌ３对ＡＰｃ的抑制作用。４－氨基吡啶（０．１ｍｍｏｌ·Ｌ－１）可逆转ＬａＣｌ３对ＡＰｃ的抑制效应。外源性乙酰胆碱引起的神经节去极化，被ＬａＣｌ３所抑制。结果提示，Ｌａ３＋可通过突触前及突触后机制抑制颈上交感神经节的突触传递。     

缺氧和/或缺糖对大鼠突触体游离钙浓度和氨基酸释放的影响

目的：研究缺氧和/或缺糖对大鼠突触体游离钙浓度和氨基酸释放的影响。方法：营养液中去除糖和/或氧，建立大鼠脑突触体缺氧、缺糖和缺血模型。检测静息及高钾去极化状态下，各种模型突触体游离钙浓度及兴奋性氨基酸(EAA)和抑制性氨基酸(IAA)释放量的变化。结果：与正常突触体相比，缺氧60min后，静息和KCl除极突触体的游离钙浓度无明显改变，而缺糖导致静息和KCl除极突触体游离钙浓度显著升高。糖和氧同时去除影响更为明显。缺氧和/或缺糖对大鼠突触体氨基酸释放的影响与此相似，缺糖对突触体氨基酸释放的影响比缺氧更明显。其中EAA门冬氨酸和IAA甘氨酸、牛磺酸、γ-氨基丁酸释放量明显增加。而谷氨酸亦有增加趋势。结论：缺糖和缺氧在缺血致脑损伤中的机制可能不同，其中缺糖有更为重要的作用。缺糖和/或缺氧致脑损伤过程中IAA的增加可能是机体的一个自我保护机制。     

箭毒对神经肌肉接头的突触前和突触后作用

<正> 已知箭毒(d—tubocurarine,d—TC)既有典型的突触后抑制作用,又有明显的影响突触前递质释放的作用。但在同一标本上同时定量比较其突触前和突触后的作用则尚未见报道,对d—TC突触前作用的性质也无统一看法。我们在大白鼠离体不均匀牵张膈肌标本上,用细胞内微电极同时记录运动终板区的微终板电位(MEPP)、终板电位(EPP) 和微电泳外源性乙酰胆碱(ACh)诱发的乙酰胆碱电位(AChP),并以AChP幅     

Facilitation and inhibition of nicotinic transmission by eserine in the sympathetic ganglia of the rabbit

The effects of eserine on neurons and on ganglionic transmission of the isolated superior cervical ganglia of the rabbit were investigated by means of intracellular recording techniques. At the concentration of 10 microM or less, eserine reversibly increased the amplitude and duration of the fast excitatory postsynaptic potential (f-epsp) induced by preganglionic nerve stimulation and of the membrane depolarization evoked by iontophoretically-applied acetylcholine (ACh), but not carbachol. At the concentration of 50 microM or more, eserine consistently and reversibly depressed the fast excitatory postsynaptic potential as well as the depolarization induced by iontophoretic application of either ACh or carbachol. Furthermore, depolarization by ACh evoked in a low Ca/high Mg solution, which blocked the liberation of transmitter was similarly reduced by eserine in greater concentrations. The passive membrane properties of the sympathetic neurons were not significantly altered by eserine in the majority of neurons studied. The results indicate that the facilitatory action of eserine on ganglionic transmission may be explained by its anticholinesterase activity, whereas eserine-induced block of transmission appears to be related to a direct interaction between the compound and the postsynaptic ACh receptor-channel complex.     

吡喹酮对神经肌肉接头传递的作用

吡喹酮可使电刺激腓总神经所引起的胫前肌收缩反应明显加强。如给腓总神经施加超强刺激,静脉注射筒箭毒碱可减弱肌肉收缩反应,吡喹酮却能加强筒箭毒碱的抑制作用,使神经肌肉传递迅即完全阻断。采用微电极细胞内记录技术研究吡喹酮对离体大鼠膈神经隔肌的作用,发现吡喹酮不明显影响膈肌细胞的静息膜电位。低浓度吡喹酮(2×10^-4M)可使微终板电位(mepp)频率明显增加。高浓度吡喹酮8×10^-4M则使mepp振幅逐渐变小和消失。吡喹酮在使神经肌肉传递阻滞不断加深的同时,尚能使终板电位的振幅变小,终致完全消失。     

Inhibition of ACh release by prostaglandin E1 in the rabbit superior cervical ganglion

Superfusion of prostaglandin E₁ (PGE₁) in low concentrations (0.01–0.5 μM) to the neurons of isolated rabbit superior cervical ganglia reversibly depressed the amplitude of the fast excitatory postsynaptic potential (f-epsp) evoked by preganglionic nerve stimulation without changing the resting membrane potential or the membrane resistance. In concentrations higher than 1 μM, PGE₁ elicited a slow membrane depolarization accompanied by a reduction in membrane resistance. PGE₁ in concentrations that did not alter the membrane potential reduced significantly the f-epsp without affecting the acetylcholine (ACh) potential induced by iontophoretic application of ACh to the ganglion cells. The results suggest that the primary action of PGE₁ in the sympathetic ganglia is to depress synaptic transmission by reducing the amount of ACh liberated from preganglionic fibers.     

The mechanism of the inhibitory action of adrenaline on transmitter release in bullfrog sympathetic ganglia: independence of cyclic AMP and calcium ions.

The effects of adrenaline and dibutyryl adenosine 3':5' - cyclic monophosphate (db cyclic AMP) on nicotinic transmission in bullfrog sympathetic ganglia were compared by use of an intracellular recording technique. The evoked release of transmitter, acetylcholine (ACh), was decreased in the presence of adrenaline (10-100 microM), while the postsynaptic sensitivity to ACh was unchanged (10 microM adrenaline) or slightly reduced (100 microM). Transmitter release was similarly inhibited by dopamine (10 microM), but not by isoprenaline (10 microM). The inhibitory action of adrenaline on transmitter release was blocked by phenoxybenzamine but not by propranolol. The inhibition of transmitter release was independent of the external calcium concentration. The evoked release of transmitter and the electrical properties of the postsynaptic membrane were unchanged during exposure to db cyclic AMP (1-4 mM), while the postsynaptic sensitivity to ACh was slightly but significantly depressed. The spontaneous release of transmitter in a high K+ (10 mM) solution was decreased in the presence of adrenaline (100-300 microM), but unchanged with db cyclic AMP (4 mM). In contrast to the effects during exposure, both the evoked and spontaneous release of transmitter were enhanced after the removal of adrenaline or db cyclic AMP. Neither adrenaline (100 microM) nor db cyclic AMP (4 mM) affected the presynaptic spike and synaptic delay. It is concluded that adrenaline mainly inhibits the release of ACh from the presynaptic terminals through its alpha-action, while db cyclic AMP reduces slightly the postsynaptic sensitivity to ACh and that both agents facilitate transmitter release when they are removed from the presynaptic terminals. It is further suggested that the inhibitory action of adrenaline is independent of endogenous cyclic AMP and calcium ions.     

Inhibition of calcium spikes and transmitter release by gamma-aminobutyric acid in the guinea-pig myenteric plexus

The effect of gamma-aminobutyric acid (GABA) (1 microM-1 mM) on synaptic transmission in isolated myenteric ganglia of guinea-pig ileum was investigated with intracellular recording techniques. GABA (up to 1 mM) had no effect on the resting membrane potential and membrane conductance of S neurones. GABA reduced the amplitude of the fast excitatory postsynaptic potential e.p.s.p.) without changing the amplitude of the nicotinic response to ionophoretic application of acetylcholine (ACh). This effect was mimicked by baclofen (10-100 microM) and was not blocked by bicuculline (10 microM). The preparation did not become desensitized during prolonged GABA applications. Cholinergic and non-cholinergic slow e.p.s.ps evoked by single or repetitive presynaptic nerve stimulation were reduced in amplitude by GABA. GABA did not depress muscarinic responses to ionophoretic application of ACh. GABA reduced the duration of the action potential in AH neurones in concentrations that did not affect the membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and tetrodotoxin was in the superfusing solution. This effect was also mimicked by baclofen, was insensitive to bicuculline and was not reduced with repeated application or GABA. It is concluded that GABA inhibits release of ACh and the transmitter mediating the slow e.p.s.p. This effect may result from inhibition of an inward calcium current.     

The effects of an adenylate cyclase inhibitor on the electrophysiological correlates of neuromuscular transmission in the frog.

The presynaptic and postsynaptic effects of MDL 12,330A, an adenylate cyclase inhibitor in several biological tissues, were studied at motor endplates in frog cutaneous pectoris nerve-muscle preparations. This agent increased both spontaneous quantal acetylcholine (ACh) release and neurally-evoked ACh release approximately twofold during the first 20-40 min of application. The increased ACh release was accompanied by a profound irreversible depression in the amplitudes of the miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps). The response to iontophoretically-applied ACh was reduced in parallel with the amplitude of the spontaneous m.e.p.ps, indicating that the depression of synaptic transmission was postsynaptic in origin. Endplates were voltage-clamped to study the postsynaptic depression in more detail. It was observed that the peak endplate current (e.p.c.) was depressed without concomitant changes in: the kinetics of e.p.c. decay, the relationship between peak e.p.c. and membrane potential, the ACh equilibrium potential or the voltage sensitivity of the e.p.c. decay. This suggests that MDL 12,330A reduces the postsynaptic sensitivity to ACh by a voltage-dependent block of the cholinoceptor. The presynaptic enhancement and the postsynaptic depression of junctional transmission produced by MDL 12,330A are discussed in conjunction with current theories of the role of adenylate cyclase and cyclic nucleotides at nicotinic cholinergic synapses.     

The mechanism of the anti-desensitizing action of sodium fluoride at the amphibian neuromyal junction

Sodium fluoride was shown in these laboratories to facilite neuromyal transmission and to be a unique antagonist of desensitization. Possible mechanisms of action of sodium fluoride include a receptor effect and chelating activity. This study concerns the mechanism of the effect of sodium fluoride (0.1–2 mM) on the desensitization of the amphibian neuromyal junction and the interaction between this mechanism and calcium. Desensitization was obtained either by repetitive (10–50 Hz), brief (2 msec) iontophoretic pulses of acetylcholine (ACh), prolonged (40 sec) iontophoretic or bath application of ACh, or repetitive (10–50 Hz) presynaptic stimulation. Microelectrode and voltage-clamp methods were employed. The rate constant of desensitization induced by repetitive pulses of ACh was calculated in terms of the decay of current or potential. It depended on the frequency of pulses and on calcium ion concentration. In low calcium solution, a high frequency of pulses had to be employed to induce desensitization with a measurable rate constant. Sodium fluoride slowed down the rate of desensitization, and increased the amplitude of ACh current or potential during desensitization. The effect of sodium fluoride on the desensitization rate was pronounced at normal and low calcium ion concentrations and was slight in high calcium solutions. Desensitization did not affect reversal potential whether the latter was evaluated in terms of ACh potentials or ACh currents, and whether desensitization was induced by repeated ACh pulses or ACh perfusion. Nor did sodium fluoride (0.5–2 mM) affect the reversal potential of either a normal or desensitized endplate.Desensitization prolonged the decay time of the excitatory postsynaptic current (EPC) without affecting the slope of the decay time-membrane voltage relationship; sodium fluoride (0.1–2 mM) further prolonged decay time without affecting membrane voltage-decay time relation. The relationship between EPC or ACh current on the one hand and membrane voltage on the other was studied with respect to desensitization, sodium fluoride, and calcium concentration. Desensitization induced by repetitive (30 Hz) presynaptic stimulation did not affect the linearity of EPC-membrane voltage relationship; this remained true in different calcium solutions and when desensitization was induced in the presence of sodium fluoride. However, desensitization attenuated the slope of this relationship, the effect being similar in all three calcium solutions. This lack of effect of calcium on the slope must be considered with respect to calcium dependence of ACh release and, thus, on the EPC amplitude. The attenuation by desensitization of the slope of the EPC-voltage relationship was antagonized by sodium fluoride. Different frequencies of ACh pulses had to be employed to induce desensitization in the three calcium solutions in order to elicit desensitization with measurable rate constant. Also in this case, the ACh current-membrane voltage remained linear before and following desensitization in the three concentrations of calcium. Again, the slope of the current-voltage relationship was attenuated by desensitization at all concentrations of calcium. Sodium fluoride antagonized this effect to a significant degree at all concentrations of calcium; the antagonism was more pronounced at low than at high concentration of calcium. Desensitization induced by ACh perfusion did not affect the linearity of ACh current-membrane voltage at either of the three calcium concentrations. In this case also, desensitization attenuated the slope of the relationship in a calcium-dependent manner. Again, sodium fluoride restored significantly the amplitude of ACh current, the recovery being well-nigh complete in low, and amounting to 44% in high calcium solution. The EGTA (see Methods) did not affect the linearity of EPC-voltage or ACh current-voltage relationship, but decreased its slope; EGTA further diminished the slope of these relationships after the slope was attenuated by desensitization induced by repetitive presynaptic stimulation or ACh pulses. At that time, sodium fluoride restored to a significant degree the slope of ACh current-membrane voltage relationship; thus, sodium fluoride and EGTA exerted opposite effects on the slope of this relationship. These results support the notion that both desensitization and the effect of sodium fluoride concern the receptor rather than the channel. They also show that while calcium is involved in desensitization and the action of sodium fluoride, the anti-desensitizing effect of sodium fluoride does not depend on its chelating effect.     

眼镜蛇神经毒素对豚鼠颈上神经节烟碱传递的易化作用(英文)

本研究用离休豚鼠颈上神经节细胞内生物电记录技术,对眼镜蛇毒神经毒素对交感神经节突触传递影响进行探讨。研究首次表明,眼镜蛇神经毒素对交感神经突触前ACh的释放有易化作用。     

Action of enflurane on cholinergic transmission in identified Aplysia neurones.

Effects of enflurane on the cholinergic transmission in Aplysia neurones were studied by current and voltage clamp methods. Acetylcholine (ACh) evoked three types of postsynaptic responses on different identified neurones: (1) a depolarizing response due to an increase in Na and K conductances (D-response), (2) a fast hyperpolarizing response due to an increase in C1 conductance (C1-response), and (3) a slow hyperpolarizing response due to an increase in K conductance (K-response). Enflurane altered neither the action potential nor the membrane resistance of the neurones but depressed the three ACh-induced responses, non-competitively, in a dose-dependent manner. The K-response was less suppressed than the other two. Blockade of the closed state of ion channel was suggested by a reduction in the first ACh response evoked 1 min after administration of enflurane. The anaesthetic facilitated the decay of the neurally evoked e.p.s.c. and i.p.s.c. in suggesting a reduction in the mean open time of the postsynaptic ion channel. It is concluded that enflurane depresses excitatory and inhibitory cholinergic transmission by reducing the postsynaptic currents.