Regulation of single potassium channels by serotonin in the cell bodies of the tail mechanosensory neurons ofAplysia californica

Sensory neurons in the pleural ganglion ofAplysia mediate the afferent portion of the tail withdrawal reflex. Previous work has shown that in these neurons and in the siphon sensory neurons ofAplysia, serotonin modulates a steady-state non-inactivating potassium current called the S current. Using the technique of patch clamping, we have examined the kinetics of single potassium channels and found that they share the properties of the S potassium channel of the siphon sensory neurons. This channel has an elementary slope conductance of73 ± 9.98pS(x±S.E.M.) and shows Goldman rectification. It is active at the resting potential and does not inactivate with maintained depolarization. Bath application of serotonin in a majority of experiments decreased the functional number of channels in the patch.     

Immunoregulatory Effect of Substance P in Human Eosinophil Migratory Function

Substance P (SP) is a tachykinin involved in the regulation of inflammatory processes. To investigate a modulatory role of the neuropeptide SP in allergic inflammation, we studied its priming effect on human eosinophil chemotaxis and kinetic responses towards platelet activating factor (PAF) and recombinant human interleukin 5 (rhlL-5). Blood was obtained from normal subjects and eosinophils were separated by Percoll discontinuous density gradient centrifugation. High purification was obtained by negative selection procedure (CD16-beads) and the experiments were performed in a 48-well microchemotaxis Boyden chamber. In the present study we demonstrate a potent synergistic effect of 100nM dose of SP on the migratory function of human eosinophils stimulated by PAF and rhIL-5. This synergism was chemotaxis specific and was abolished by NK-1 receptor antagonist (FK888). The results suggest that neurogenic stimuli may play a significant role in eosinophil infiltration via its priming effect on the cell.     

模拟脑电节律的调制磁场对中缝核神经元放电影响的研究

用数值计算和动物实验的方法研究模拟脑电节律的调制磁场对与睡眠有关的中缝核神经元放电的影响 ,从而探讨其对睡眠的影响。通过数字仿真 ,研究了神经纤维对调制磁场刺激作用的响应特性 ,发现了神经纤维具有对低频调制包络信号响应敏感 ,对高频载波不响应的特性。依据睡眠全过程脑电节律的变化 ,研制了模拟 EEG信号发生器。采用高频磁脉冲作为载波调制模拟脑电节律信号 ,用所得的调制磁场诱导兔脑 ,观察磁刺激对中缝核5 -羟色胺能神经元放电的影响。动物实验结果表明 ,中缝核经磁刺激后放电频率发生显著改变 ,其放电变慢。这说明磁刺激能抑制 5 -羟色胺能神经元神经电活动水平 ,将为改善失眠症提供新的途径     

一种更接近X线管焦点MTF的抽样函数

本文提出了一种线扩散函数，用以从理论上估算Ｘ线管的ＭＴＦ。结果表明较脉冲函数更加实际，而且在空间频率较大的区域也较准确。     

Description of Heart-Rate Variability Data in Accordance With a Physiological Model for the Genesis of Heartbeats

A survey is presented of techniques which transform heart-rate variability data into a signal that is both visually informative and accessible for analysis. The Instantaneous Heart-Rate (IHR) signal is introduced, i.e. the signal having the value of the heart rate (inverse interbeat interval) during the interval concerned. The IHR signal differs from the standard Delayed Heart-Rate (DHR) signal, which is always one beat late. The relationship is discussed between the different representation methods and the Integral Pulse Frequency Modulation (IPFM) model, the latter being a physiologically plausible model for the transformation of a continuous input signal (e.g., nervous influence on the cardiac pacemaker) into a series of events (heartbeats). It is shown that when the IHR signal is used as input of the IPFM model, the event series from which the signal was derived appears at the output. Hence, if the IPFM model is accepted as a model of the pacemaker, the IHR signal may be considered as an approximation of the neural (sympathetic and parasympathetic) influence on the pacemaker. In addition we show that the appearance of the IHR signal is less affected by trigger errors or extrasystoles than the standard DHR signal. It is concluded that the most attractive time-domain representation of physiological event series consists of the IHR signal, because this signal, being conceptually and computationally simple, is consistent with the IPFM model.     

Control of locomotion in the marine mollusc Clione limacina

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5×10^-7 to 1×10^-6 M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.     

Phase I and pharmacokinetics studies of prochlorperazine 2-h i.v. infusion as a doxorubicin-efflux blocker

In an earlier phase I study, we reported that the maximal tolerated dose (MTD) of prochlorperazine (PCZ) given as a 15-min i.v. infusion was 75 mg/m². The highest peak plasma PCZ concentration achieved was 1100 ng/ml. The present study was conducted to determine if PCZ levels high enough to block doxorubicin (DOX) efflux in vitro could be achieved and sustained in vivo by increasing the duration of i.v. infusion from 15 min to 2 h. The treatment schedule consisted of i.v. prehydration with at least 500 ml normal saline (NS) and administration of a fixed standard dose of 60 mg/m² DOX as an i.v. bolus over 15 min followed by i.v. doses of 75, 105, 135, or 180 mg/m² PCZ in 250 ml NS over 2 h. The hematologic toxicities attributable to DOX were as expected and independent of the PCZ dose. Toxicities attributable to PCZ were sedation, dryness of mouth, anxiety, akathisia, hypotension, cramps, and confusion. The MTD of PCZ was 180 mg/m². Large interpatient variation in peak PCZ plasma levels (91–3215 ng/ml) was seen, with the plasma half-life (t1/2) being approximately 57 min in patients given 135–180 mg/m² PCZ. The volume of distribution (V_d), total clearance (Cl_T), and area under the curve (AUC) were 350.1±183.8 l/m², 260.7±142.7 l m² h^–1 and 1539±922 ng ml h^–1, respectively, in patients given 180 mg/m² PCZ and the respective values for patients receiving 135 mg/m² were 48.9±23.76 l/m², 33.2±2.62 l m² h^–1, and 4117±302 ng ml h^–1. High PCZ plasma levels (>600 ng/ml) were sustained in all patients treated with 135 mg/m² PCZ for up to 24 h. DOX plasma elimination was biphasic at 135 and 180 mg/m² PCZ, and a>10-ng/ml DOX plasma level was maintained for 24 h. Partial responses were seen in three of six patients with malignant mesothelioma, in two of ten patients with non-small-cell lung carcinoma, and in the single patient with hepatoma. Our data show that PCZ can be safely given as a 2-h infusion at 135 mg/m² with clinically manageable toxicities. The antitumor activity of the combination of DOX and PCZ needs to be confirmed in phase II trials.This work was supported by NIH grant R01 CA-29360 and S1488, CRC grant M01 RR-05280, and the Joan Levy Cancer Foundation. This paper was presented at the meeting of the American Association for Cancer Research, Orlando, Florida, May 19–22, 1993     

Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.     

Potassium channels in crustacean glial cells.

Unitary currents through single ion channels in the glial cells, which ensheath the abdominal stretch receptor neurons of the crayfish, were characterized with respect to their basic kinetic properties. In cell-attached and excised patches two types of Ca(++)-independent K+ channels were observed with slope conductances of 57 pS and 96 pS in symmetrical K+ solution. The 57 pS K+ channel was weakly voltage-dependent with a slope of the Po vs. membrane potential relationship of +95 mV for an e-fold change in Po. In addition to the main conductance level, the channel displayed conductance levels of 80 and 109 pS. In excised patches, channel activity of this "subconductance" K+ channel showed "rundown" that could be prevented with 2 mM ATP-Mg on the cytoplasmic side of the membrane. The 96 pS K+ channel was strongly voltage-dependent with a slope of +12 mV for an e-fold change in Po. Averaged single-channel currents elicited by voltage jumps proved the channel to be of the delayed rectifying type. Channel activity persisted in excised patches with minimal salt solution and in virtually Ca(++)-free saline. Because of its dependence on intracellular ATP-Mg, the subconductance K+ channel is discussed as a target of modulation by transmitters or peptides via phosphorylation of the channel.     

Modulation in time of the interictal spiking pattern related to epileptic seizures

ObjectiveTo test the hypothesis that significant changes in the occurrence of interictal epileptiform electroencephalography (EEG) discharges (EDs) are associated with seizures: while some EDs are pro-convulsive, increasing at seizure-occurrence, others are protective, showing decrease related to seizures.MethodsWe analyzed 102 consecutive, long-term video-EEG monitoring sessions, from 98 patients. Using a semi-automated spike-detection method, we quantified the occurrence of EDs, grouped according to their location and morphology (clusters) and we constructed graphical representation of data, showing changes in time of the spiking patterns (spike-histograms). We compared the spike-histograms with the time-points of the seizures (pre-, peri- and postictal changes).ResultsTotally 179 ED-clusters were identified. Modulation of the spiking pattern, associated with seizures, was observed in 66 clusters (37%), from 47 patients (48%). Most of these changes (40 clusters; 61%) were related to increase in the spiking-pattern.ConclusionsChanges in spiking-pattern were associated with more than one third of the EDs. Both increasing and decreasing patterns were observed.SignificanceEDs are more often pro-convulsive, with increasing spiking patterns associated with seizures. However, in more than one third of the ED clusters modulated by seizures, the spiking pattern decreased, raising the possibility of an anticonvulsive function of these discharges.