The molecular basis of acid insensitivity in the African naked mole-rat

Acid evokes pain by exciting nociceptors; the acid sensors are proton-gated ion channels that depolarize neurons. The naked mole-rat (Heterocephalus glaber) is exceptional in its acid insensitivity, but acid sensors (acid-sensing ion channels and the transient receptor potential vanilloid-1 ion channel) in naked mole-rat nociceptors are similar to those in other vertebrates. Acid inhibition of voltage-gated sodium currents is more profound in naked mole-rat nociceptors than in mouse nociceptors, however, which effectively prevents acid-induced action potential initiation. We describe a species-specific variant of the nociceptor sodium channel Na(V)1.7, which is potently blocked by protons and can account for acid insensitivity in this species. Thus, evolutionary pressure has selected for an Na(V)1.7 gene variant that tips the balance from proton-induced excitation to inhibition of action potential initiation to abolish acid nociception.     

The cell and molecular basis of mechanical, cold, and inflammatory pain

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Na(v)1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.     

Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury

The mechanisms by which peripheral nerve injuries sometimes lead to causalgia, aberrant burning pain peripheral to the site of nerve damage, are uncertain, although the sympathetic nervous system is known to be involved. Whether such syndromes could be the result of the development of responsiveness by some cutaneous pain receptors (C-fiber nociceptors) to sympathetic efferent activity as a consequence of the nerve injury was tested in an animal model. After nerve damage but not in its absence, sympathetic stimulation and norepinephrine were excitatory for a subset of skin C-fiber nociceptors and enhanced the responsiveness of these nociceptors to tissue-damaging stimulation. These effects were demonstratable within days after nerve lesions, occurred at the cutaneous receptive terminal region, were manifest in sensory fibers that had not degenerated after the injury, and were mediated by alpha 2-adrenergic-like receptors.     

Sodium current in ventricular myocardial fibers

Membrane currents were measured in thin bundles of dog ventricular myocardium under voltage-clamp conditions. A rather large initial inward current which had an equilibrium potential at about + 55 millivolts could be recorded. When the external sodium concentration was reduced, the equilibrium potential for this current was shifted by the amount predicted theoretically for a current carried solely by sodium ions. The size of the sodium inward current (I(Na)) was largely dependent on the preceding membrane potential. The I(Na) was completely inactivated if the membrane potential was as low as -45 millivolts. Sodium ions are the main carrier of charge during the rapid depolarization phase of the action potential.     

急性心肌缺血大鼠左心室流出道自发性慢反应电位去极离子流变化分析

目的探讨急性心肌缺血大鼠左室流出道自发性慢反应电位去极离子流的变化。方法常规玻璃微电极细胞内方法观测急性心肌缺血大鼠的离体心脏最大舒张电位(MDP)、0相除极幅度(APA)、0相最大除极速度(Vmax)、4相自动除极速度(VDD)、复极50%(APD50)和90%(APD90)的时间以及自发放电频率(RPF)。结果与给药前相比①1.2mmol.L-1河豚毒(TTX)使APA和Vmax有所减小(P<0.05),VDD和RPF明显减慢(P<0.01);②1.0μmol.L-1维拉帕米(VER)可使该慢电位的APA、Vmax、VDD明显减小,RPF减慢(P<0.01);APD、APD90延长(P<0.05);③2mmol.L-1 4-氨基吡啶(4-AP)使该慢电位的MDP的绝对值、APA、Vmax减小,VDD和RPF加快(P<0.01);④1.5mmol.L-1 CsCl作用6min时,VDD和RPF明显降低(P<0.05),10min时恢复。结论①左心室流出道的自发慢电位0相主要去极离子流除Ca2+内流外,还有少量Na+内流。②4相去极离子流中,除Ca2+、Na+的内流和Ik衰减外,If电流可能也起部分作用。     

A low threshold calcium spike mediates firing pattern alterations in pontine reticular neurons

Intracellular electrical recordings in an in vitro slice preparation of the brainstem medial pontine reticular formation, a region thought to be important in mediation of desynchronized sleep phenomena, demonstrate a population of neurons that have a calcium-dependent, low threshold spike. This low threshold spike was inactivated at relatively depolarized membrane potential levels and, when this spike was deinactivated, it induced a burst of action potentials. The membrane potential dependence of the spike may underlie changes in action potential firing patterns associated with behavioral state change because the baseline membrane potential in neurons of the medial pontine reticular population depolarizes during passage from waking and slow wave sleep to desynchronized sleep, which is characterized by the absence of burst firing.     

Both mu and delta opiate receptors exist on the same neuron

Low concentrations of the relatively selective opiate receptor agonists dihydromorphine and normorphine (mu receptor agonists) and D-Ala 2-D-Leu 5-enkephalin (a delta receptor agonist) were applied to single enteric neurons while the frequency of action potential firing was recorded. Most neurons that were inhibited by the mu agonists were also inhibited by the delta agonist, but the two receptors could be distinguished by the higher concentration of naloxone required to antagonize the delta agonist. The results indicate that enteric neurons bear both mu and delta receptors and that cell firing is inhibited if either receptor type is activated.     

木薯醇腈酶在枯草芽孢杆菌中的表达及活性检测

醇腈酶(α-hydroxynitrile lyase,HNL)能够催化羰基化合物和HCN立体选择性的加工形成手性醇腈化合物。以含有木薯醇腈酶基因的重组质粒pET28a-HNL为模板,应用PCR扩增得到HNL基因,将其连接到pMD18-T载体中进行测序分析,然后通过Nde I和Xba I2个酶切位点将其连接到枯草芽孢杆菌表达载体pMA5Z2中,获得了含有HNL基因的重组质粒pMA5Z2-HNL,转化蛋白质三缺陷的枯草芽孢杆菌DB1342。SDS-PAGE显示HNL在枯草芽孢杆菌DB1342中获得表达,产物分泌到细胞外,每毫升发酵液中获得了2.108 U的醇腈酶。     

Firing patterns of hypothalamic supraoptic neurons during water deprivation in monkeys

Water deprivation in monkeys caused an acceleration of action potential firing of supraoptic neurons, but not of neurons located 2 to 3 millimeters above the hypothalamic supraoptic nucleus. Whereas in the normally hydrated animal only 12 percent of the neuroendocrine cells discharged periodically, the proportion of these periodic bursters increased markedly with increasing plasma osmolarity. This finding suggests that such periodically firing supraoptic neurons are those engaged in active neurohypophyseal hormone secretion.     

MHC class I peptides as chemosensory signals in the vomeronasal organ

The mammalian vomeronasal organ detects social information about gender, status, and individuality. The molecular cues carrying this information remain largely unknown. Here, we show that small peptides that serve as ligands for major histocompatibility complex (MHC) class I molecules function also as sensory stimuli for a subset of vomeronasal sensory neurons located in the basal Gao- and V2R receptor-expressing zone of the vomeronasal epithelium. In behaving mice, the same peptides function as individuality signals underlying mate recognition in the context of pregnancy block. MHC peptides constitute a previously unknown family of chemosensory stimuli by which MHC genotypic diversity can influence social behavior.     

苦杏仁精油对白纹伊蚊的驱避活性研究

采用个体涂肤有效保护时间试验研究了苦杏仁精油对白纹伊蚊的驱避活性。结果表明,含HCN和去除HCN的苦杏仁精油对白纹伊蚊都具有很强的驱避活性,涂药8h后,2种苦杏仁精油对白纹伊蚊的驱避率均在96.76%以上,作为对照的隆力奇花露水的驱避率为58.28%。另外,2种精油对人体的有效保护时间分别为6h和7h,高于隆力奇花露水4h。可见苦杏仁精油对白纹伊蚊具有很强的驱避效果,且其有效保护时间高于隆力奇花露水,因而有望开发成为新型的蚊虫驱避剂。     

Differential shunting of EPSPs by action potentials

Neurons encode information and communicate via action potentials, which are generated following the summation of synaptic events. It is commonly assumed that action potentials reset the membrane potential completely, allowing another round of synaptic integration to begin. We show here that the conductances underlying the action potential act instead as a variable reset of synaptic integration. The strength of this reset is cell type-specific and depends on the kinetics, location, and timing of the synaptic input. As a consequence, distal synapses, as well as inputs mediated by N-methyl-d-aspartate receptor activation, can contribute disproportionately to synaptic integration during action potential firing.     

The twitch in horses: a variant of acupuncture

The twitch procedure in horses attenuates the increase in the heart rate evoked by pain-inducing stimuli and the reaction of the animals to such stimuli. Endorphin systems are probably involved in the effectiveness of the twitch, since its action is blocked by naloxone and its application increases plasma concentrations of immunoreactive beta-endorphin. The mode of action of the twitch cannot be explained by the generally accepted theory of divertive pain and may resemble that of classical acupuncture.     

Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition

Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.     

枣雄性不育种质半同胞子代的遗传多样性分析

以280份种质,包括枣的雄性不育种质JMS2、‘交城五号’枣、‘邢16’酸枣、JMS2ב交城五号’的56个子代、JMS2ב邢16’的96个子代以及JMS2自然授粉获得的125个子代为材料,采用SSR分子标记技术研究枣半同胞家系的遗传多样性。10对SSR引物在277份子代中检测出35个等位基因,观测等位基因数量(Na)、有效等位基因数量(Ne)、香侬指数(I)、观测杂合度(Ho)、期望杂合度(He)、基因遗传多样性(h)和基因分化系数(Fst)分别为3.500,2.108 7,0.819 2,0.573 1,0.471 4,0.470 5和0.096 0,表明277个子代的遗传多样性水平一般。在以JMS2为母本的3个子代群体中,未知父本的自然杂交子代群体遗传多样性最为丰富,I、Na和Ne分别为0.749 5,3.500 0,2.029 2。JMS2ב邢16’子代群体的遗传多样性(Na=2.30,Ne=2.067 8,I=0.722 0)小于自然杂交子代群体,但大于JMS2ב交城五号’子代群体(Na=2.3,Ne=1.829 3,I=0.615 9)。JMS2自然授粉子代可能存在多个父本,JMS2与酸枣‘邢16’较JMS2和‘交城五号’的亲缘关系远,双亲亲缘关系远和多个父本授粉可增加JMS2半同胞子代的遗传多样性。本研究可以为进一步评价和利用枣半同胞家系提供借鉴参考。     

Odor stimuli trigger influx of calcium into olfactory neurons of the channel catfish

Olfactory transduction is thought to be mediated by a G protein-coupled increase in intracellular adenosine 3',5'-monophosphate (cAMP) that triggers the opening of cAMP-gated cation channels and results in depolarization of the plasma membrane of olfactory neurons. In olfactory neurons isolated from the channel catfish, Ictalurus punctatus, stimulation with olfactory stimuli (amino acids) elicits an influx of calcium that leads to a rapid increase in intracellular calcium. In addition, in a reconstitution assay a plasma membrane calcium channel has been identified that is gated by inositol-1,4,5-trisphosphate (IP3), which could mediate this calcium influx. Together with previous studies indicating that stimulation with olfactory stimuli leads to stimulation of phosphoinositide turnover in olfactory cilia, these data suggest that an influx of calcium triggered by odor stimulation of phosphoinositide turnover may be an alternate or additional mechanism of olfactory transduction.     

持续游泳训练对大鼠杏仁核cAMP浓度的影响

采用大鼠环磷酸腺苷cAMP ELISA法,检测持续游泳训练后大鼠杏仁核cAMP浓度变化,以探讨运动应激引起机体反应的机制。结果表明,持续游泳训练后,除1 h时cAMP浓度显著低于对照组外(P0.01),即刻、0.5 h、2 h大鼠杏仁核cAMP浓度均显著高于对照组(P0.05);训练后即刻,大鼠杏仁核cAMP浓度快速升高,至0.5 h时达到最高值,之后1 h时cAMP浓度急剧下降,2 h时其浓度回升,高于对照组的水平,随后4 h时下降至略低于对照组水平,但差异不显著。整个浓度变化曲线呈锯齿形。持续游泳训练后杏仁核cAMP浓度变化具有时相性;持续游泳训练可激活大鼠杏仁核环磷酸腺苷(cAMP)通路,进而影响机体的后续反应。     

海雀稗种质资源的耐盐性评价

对海雀稗耐盐体系进行优化，并通过测定坪用质量和枯黄率对27份海雀稗种质资源进行了耐盐性评价。结果表明，7个不同NaCl浓度（0，5，10，15，20，25，30 g·L?1）处理下，坪用质量、枯黄率和叶色各指标之间存在显著差异（P<0.05）。随着NaCl处理浓度的增加，坪用质量显著下降（P<0.05），枯黄率显著增加（P<0.05），叶色显著变浅（P<0.05）。建立回归方程，以枯黄率50%为标准，确定海雀稗最适盐处理浓度为25 g·L?1。利用25 g·L?1 NaCl对27份海雀稗种质资源进行耐盐性评价，筛选出2种极端耐盐种质:USA17-18（耐盐）和USA17-26（敏盐）。对海雀稗耐盐极端材料的钠钾离子含量进行测定，发现盐处理后，地上和地下Na+含量均显著增加，但K+含量和K/Na值都显著下降。减少Na+的摄入，维持较高的K+含量，可能是海雀稗耐盐的机制。     

Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia

Inflammation, trauma, or nerve injury may cause enduring hyperalgesia, an enhanced sensitivity to painful stimuli. Neurons in lamina I of the spinal dorsal horn that express the neurokinin 1 receptor for substance P mediate this abnormal pain sensitivity by an unknown cellular mechanism. We report that in these, but not in other nociceptive lamina I cells, neurokinin 1 receptor-activated signal transduction pathways and activation of low-threshold (T-type) voltage-gated calcium channels synergistically facilitate activity- and calcium-dependent long-term potentiation at synapses from nociceptive nerve fibers. Thereby, memory traces of painful events are retained.     

17β-Estradiol Regulates Cultured Immature Boar Sertoli Cell Proliferation via the cAMP-ERK1/2 Pathway and the Estrogen Receptor β

Estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17β-estradiol affected the proliferation of cultured, immature boar Sertoli cells via the estrogen receptor β （ERβ） and the cAMP-extracellular signal-regulated kinase （ERK1/2） pathway. Low levels （10-10-10-8 mol L-1） of 17β-estradiol increased cell number, but high levels （10-7-10-6 mol L-1） decreased it （P〈0.05）. Sertoli cell number began to recover for an additional 24 h in the medium without 17β-estradiol （10-6 mol L-l） （P〉0.05）. The effects of 17β-estradiol （10-9 mol L-1） peaked at the first 24 h （P〈0.05）. 17β-estradiol activated ERK1/2 from 5 min to 24 h, but the activiy of ERK1/2 began to decrease after 4 h. Both PD98059 and U0126, two ERK inhibitors, blocked cell division （P〈0.05）. 17β-estradiol （10-10-10-6 mol L-1） dose-dependently increased cAMP production （P 〈 0.05）, and both 17β-estradiol （10-9 mol L-1） and forskolin, which increases cAMP levels, induced cell proliferation and activated ERK1/2 （P〈 0.05）. Rp-cAMP, an antagonist of cAMP, blocked this 17β-estradiol activity （P〈 0.05）. Two estrogen receptor antagonists, ICI 182780 and ERβ antagonist （ERβAnt）, reduced Sertoli cell number, cAMP production and ERK1/2 activation （P〈 0.05）, but ERaAnt did not （P〉 0.05）. Therefore, 17β- estradiol mainly promotes pig Sertoli cell proliferation via ERβ to induce cAMP production and ERK activation to promote cell proliferation.