DOCSLIB.ORG

View Full Page

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
View Full Page The Journal of Neuroscience, May 1993, 13(5): 1976-1992 Na+ Channel lmmunolocalization in Peripheral Mammalian Axons and Changes following Nerve Injury and Neuroma Formation Marshall Devor,’ Ruth Govrin-Lippmann,’ and Kimon Angelides* ‘Department of Cell and Animal Biology, Life Sciences Institute, Hebrew University of Jerusalem, Jerusalem 91904, Israel and 2Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030 Nerve injury frequently triggers hyperexcitability and the ec- channel-rich membrane patch that servesto encode integrated topic initiation of impulses in primary afferent axons. An im- depolarizations from dendritic and somatic inputs into an ap- portant consequence is neuropathic paresthesias and pain. propriate firing pattern. Usually this encoding region lies near Electrogenesis in normal afferents depends on appropriate the cell soma: the axon hillock or the first node of Ranvier Na+ channel concentrations. Therefore, we have asked (Dodge and Cooley, 1973; Waxman and Quick, 1978; Matsu- whether injury might trigger changes in axolemmal Na+ chan- moto and Rosenbluth, 1985; Wollner and Catterall, 1986). An nel distribution that could account for neuropathic hyper- exception is the primary afferent neuron, in which this zone is excitability. We used an Na+ channel-specific antibody, 7493, displaced to the far distal end of the peripheral axon, often to immunolocalize Na+ channels ultrastructurally in mem- centimeters or even meters from the cell soma. Here it serves branes of normal rat axons, and to assess remodeling fol- as a sensorytransducer ending. lowing nerve section and neuroma formation. Selective la- The sensory end of afferent axons is highly specialized for beling of nodal axolemma and, more weakly, of Schwann translating stimulus-evoked depolarizations (generator poten- cell membrane, confirmed the efficacy of our immunolabel- tial) into spike trains. This capability is absent over the rest of ing protocol. In neuromas at postoperative times associated the axon. For example, mechanical or thermal stimulation in with peak ectopic activity, we found clear evidence of Na+ mid-nerve, or even direct injection of depolarizing current channel accumulation. Specifically, soon after myelin was through an intracellular microelectrode, doesnot yield sustained stripped from large-diameter axons, the exposed, formerly firing (Ruiz et al., 198 1). internodal axolemma became immunopositive. Small-di- In contrast to the midnerve part of intact axons, many chron- ameter unmyelinated axons and axon sprouts in the neuroma ically injured afferents are able to sustain repetitive discharge. were also marked with 7493 IgG. Activated phagocytic mac- This ectopic rhythmic firing capability develops with time at rophages and endothelial cells were 7493 negative. Both formerly mid-nerve sites, yielding foci of abnormal evoked and large- and small-diameter axons in neuromas end in swollen, spontaneousafferent discharge(Koschorke et al., 1991; Devor, organelle-packed “end bulbs.” Most, but not all, of these 1993). In recent years a good deal of evidence hasaccumulated acquired Na+ channel immunolabeling. We propose that re- establishing activity originating at such ectopic neural pace- modeling results from a modification of the normal process maker sites as an important cause of neuropathic paresthesias of Na+ channel turnover in neural membranes. Na+ channel and pain in nerve injured patients (Nystrom and Hagbarth, protein accumulates in preterminal axolemma and neuroma 1981; Ochoa et al., 1982; Nordin et al., 1984; Devor, 1993). end bulbs due to a combination of permissive factors (es- These indications of a causal link between abnormal neural pecially myelin removal) and promotional factors (removal activity and neuropathic pain motivate a searchfor the cellular of normal downstream targets). This accumulation is a likely mechanism responsiblefor the development of ectopic firing precursor of afferent hyperexcitability in injured nerve. capability in afferents. Since impulse initiation at normal lo- [Key words: ectopic hyperexcitability, membrane remod- cations is dependent on Na+ channels, we have used an Na+ eling, nerve injury, neuroma, pain, sodium channels] channel-specific antibody to look for possiblechanges in Na+ channel distribution at sites of nerve injury associatedwith The ability of neurons to initiate trains of action potentials ectopic firing. dependson the presenceof transmembraneproteins that serve as regulated channelsfor ionic current flow. A uniquely impor- Materials and Methods tant one in this process is the voltage-sensitive Na+ channel Subjects and surgery.We usedadult (>300 gm) maleWistar-derived (Hille, 1984). Most vertebrate neurons have a localized, Na+ Sabrastrain rats.Work followedethical guidelines of the International Associationfor the Study of Pain(IASP), and university and national regulationson humaneuse of researchanimals. Under Nembutalan- esthesia (50 mg/kg, i.p.), the sciatic nerve was exposed in the popliteal Received Mar. 9, 1992; revised Nov. 6, 1992; accepted Nov. II, 1992. fossaand tightly ligatedwith 5-Osilk. The nerve wasthen cut across We acknowledge the helpful comments of S. G. Waxman, J. A. Black, and M. about 1 mm distal to the ligature, andabout 5 mm of the distal stump H. Ellisman. This work was supported by grants from the United States-Israel Binational Science Foundation (BSF), the Hebrew University Center for Research wasexcised. Alternatively, the L4 and L5 dorsalroots (DRs) were ex- on Pain, the (U.S.) National Multiple Sclerosis Society, and the U.S. National posed in a lumbar laminectomy, tightly ligated with 6-O silk -3-5 mm Institutes of Health (NIH Grant CNS28072). from their point of entry into the spinal cord, and cut between the Correspondence should he addressed to Prof. Marshall Devor at the above ligatureand the cord. In somerats both lesionswere carried out. In- address. cisions were closed in layers, and topical and systemic antibiotics ad- Copyright @ 1993 Society for Neuroscience 0270-6474/93/131976-17.SO5.00/0 ministered. Recovery was uneventful. This net-ve/DR injury, designed The Journal of Neuroscience, May 1993, 73(5) 1977 to suppress regeneration and promote neuroma formation, is identical axons was disrupted and undergoing active phagocytosis,while to that used in our prior electrophysiological and anatomical studies of in others new myelin was being laid down. This zone was rich experimental neuromas (reviewed in Devor, 1993). The rats were maintained postoperatively under standard colony con- in demyelinated preterminal axon segments,swollen organelle- ditions. At appropriate times they were deeply anesthetized and perfused packed terminal “end bulbs,” and at later survival times, nu- transcardially with saline followed by 4% paraformaldehyde in 0.1 M merous preterminal axon branches and fine unmyelinated PO, buffer (37°C pH 7.4). After ~230 min postfixation in situ, tissue sprouts. (3) In the 300 pm nearest the ligature was a “zone of was removed and postfixed for an additional 2-3 hr at 4°C. In addition demyelination” in which myelin was removed without renewal. to neuromas and proximal nerve and DR segments, control samples of intact contralateral nerves and DRs were also taken. Most axon end bulbs occurred within this region, which also Immunostaining. The results are based primarily on DR and sciatic had many demyelinated axons, and a gradually increasingpop- nerve neuromas from rats that survived 7 and 13 d postoperatively, the ulation of axons sprouts. (4) Finally, under the ligature, was a interval corresponding to the peak of neuroma A-fiber hyperexcitability “compression zone” that contained few, if any, neuronal pro- (Pauir-Kricheli and Devor. 1988). Short seaments of fixed nerve, DR. and neuroma segments were quartered longytudinally using a fresh #l 1 cesses.In the present study we focused on Na+ channel im- blade, and desheathed. They were then rinsed (3 x 5 min buffer, 3 x munolocalization within the zones of dys- and demyelination 5 min buffer with 0.1 M glycine, 4”C), transferred to blocking medium in the distal 3 mm of the injured nerve. [ 1 x 10 min glycinejbuffer containing 2% normal goat serum (Sigma), 20°C], and incubated overnight in primary antibody in blocking medium Immunolabel specificity and the heterogeneousdistribution of (20°C, gentle agitation). Na+ channel epitopesin normal axons The following day tissue was rinsed in glycine/buffer and then buffer alone (both 5 x 3 min, 20°C) incubated for l-2 hr (20°C) in biotinylated Specificity. Immunolabeling using 7493 IgG occurred consis- goat anti-rabbit IgG, buffer rinsed (5 x 10 min), and reacted in ABC tently on some cell types and membrane locations, avoiding reagent (Elite kit, Vector Labs) followed by NiCl-intensified diamino- others completely (see below). There was no intracellular la- benzidine (DAB). Tissue was then postfixed in 3% glutaraldehyde, buffer rinsed overnight (4”C), osmicated (1% OsO,, 4°C) dehydrated in as- beling. Primary 7493 IgG yielded the most intense immuno- cending alcohols (4°C) and then propylene oxide (20”(Z), and embedded labeling of membranes,although with this material there was in LX-araldite. Longitudinal thin sections were picked up on copper always some decoration of basal lamina (e.g., open arrow in grids and viewed in a JEOL 1 OOCX. We usually avoided counterstaining Figs. 3A, 6A). Most ofthis can be attributed to antibodiespresent and instead used a small (40 pm) aperture and low accelerating voltage
Load more

Recommended publications
  • Nervous Tissue
    Nervous Tissue Prof.Prof. ZhouZhou LiLi Dept.Dept. ofof HistologyHistology andand EmbryologyEmbryology Organization:Organization: neuronsneurons (nerve(nerve cells)cells) neuroglialneuroglial cellscells Function:Function: Ⅰ Neurons 1.1. structurestructure ofof neuronneuron somasoma neuriteneurite a.a. dendritedendrite b.b. axonaxon 1.11.1 somasoma (1)(1) nucleusnucleus LocatedLocated inin thethe centercenter ofof soma,soma, largelarge andand palepale--stainingstaining nucleusnucleus ProminentProminent nucleolusnucleolus (2)(2) cytoplasmcytoplasm (perikaryon)(perikaryon) a.a. NisslNissl bodybody b.b. neurofibrilneurofibril NisslNissl’’ss bodiesbodies LM:LM: basophilicbasophilic massmass oror granulesgranules Nissl’s Body (TEM) EMEM:: RERRER,, freefree RbRb FunctionFunction:: producingproducing thethe proteinprotein ofof neuronneuron structurestructure andand enzymeenzyme producingproducing thethe neurotransmitterneurotransmitter NeurofibrilNeurofibril thethe structurestructure LM:LM: EM:EM: NeurofilamentNeurofilament micmicrotubulerotubule FunctionFunction cytoskeleton,cytoskeleton, toto participateparticipate inin substancesubstance transporttransport LipofuscinLipofuscin (3)(3) CellCell membranemembrane excitableexcitable membranemembrane ,, receivingreceiving stimutation,stimutation, fromingfroming andand conductingconducting nervenerve impulesimpules neurite: 1.2 Dendrite dendritic spine spine apparatus Function: 1.3 Axon axon hillock, axon terminal, axolemma Axoplasm: microfilament, microtubules, neurofilament, mitochondria,
    [Show full text]
  • Pre-Oligodendrocytes from Adult Human CNS
    The Journal of Neuroscience, April 1992, 12(4): 1538-l 547 Pre-Oligodendrocytes from Adult Human CNS Regina C. Armstrong,lJ Henry H. Dorn, l,b Conrad V. Kufta,* Emily Friedman,3 and Monique E. Dubois-Dalcq’ ‘Laboratory of Viral and Molecular Pathogenesis, and %urgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892 and 3Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104-3246 CNS remyelination and functional recovery often occur after Rapid and efficient neurotransmission is dependent upon the experimental demyelination in adult rodents. This has been electrical insulating capacity of the myelin sheath around axons attributed to the ability of mature oligodendrocytes and/or (reviewed in Ritchie, 1984a,b). Nerve conduction is impaired their precursor cells to divide and regenerate in response after loss of the myelin sheath and results in severe neurological to signals in demyelinating lesions. To determine whether dysfunction in human demyelinating diseases such as multiple oligodendrocyte precursor cells exist in the adult human sclerosis (MS). Remyelination can occur in the CNS of MS CNS, we have cultured white matter from patients under- patients but appears to be limited (Perier and Gregoire, 1965; going partial temporal lobe resection for intractable epilep- Prineas et al., 1984). Studies of acute MS cases have revealed sy. These cultures contained a population of process-bear- that recent demyelinating lesions can exhibit remyelination that ing cells that expressed antigens recognized by the 04 appears to correlate with the generation of new oligodendrocytes monoclonal antibody, but these cells did not express galac- (Prineas et al., 1984; Raine et al., 1988).
    [Show full text]
  • Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury Rachel E
    Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 Acute reduction of microglia does not alter axonal injury in a mouse model of repetitive concussive traumatic brain injury Rachel E. Bennett Washington University School of Medicine David L. Brody Washington University School of Medicine Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Bennett, Rachel E. and Brody, David L., ,"Acute reduction of microglia does not alter axonal injury in a mouse model of repetitive concussive traumatic brain injury." Journal of Neurotrauma.31,9. 1647-1663. (2014). https://digitalcommons.wustl.edu/open_access_pubs/4711 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. JOURNAL OF NEUROTRAUMA 31:1647–1663 (October 1, 2014) ª Mary Ann Liebert, Inc. DOI: 10.1089/neu.2013.3320 Acute Reduction of Microglia Does Not Alter Axonal Injury in a Mouse Model of Repetitive Concussive Traumatic Brain Injury Rachel E. Bennett and David L. Brody Abstract The pathological processes that lead to long-term consequences of multiple concussions are unclear. Primary mechanical damage to axons during concussion is likely to contribute to dysfunction. Secondary damage has been hypothesized to be induced or exacerbated by inflammation. The main inflammatory cells in the brain are microglia, a type of macrophage. This research sought to determine the contribution of microglia to axon degeneration after repetitive closed-skull traumatic brain injury (rcTBI) using CD11b-TK (thymidine kinase) mice, a valganciclovir-inducible model of macrophage depletion.
    [Show full text]
  • Was Not Reached, However, Even After Six to Sevenhours. A
    PROTEIN SYNTHESIS IN THE ISOLATED GIANT AXON OF THE SQUID* BY A. GIUDITTA,t W.-D. DETTBARN,t AND MIROSLAv BRZIN§ MARINE BIOLOGICAL LABORATORY, WOODS HOLE, MASSACHUSETTS Communicated by David Nachmansohn, February 2, 1968 The work of Weiss and his associates,1-3 and more recently of a number of other investigators,4- has established the occurrence of a flux of materials from the soma of neurons toward the peripheral regions of the axon. It has been postulated that this mechanism would account for the origin of most of the axonal protein, although the time required to cover the distance which separates some axonal tips from their cell bodies would impose severe delays.4 On the other hand, a number of observations7-9 have indicated the occurrence of local mechanisms of synthesis in peripheral axons, as suggested by the kinetics of appearance of individual proteins after axonal transection. In this paper we report the incorporation of radioactive amino acids into the protein fraction of the axoplasm and of the axonal envelope obtained from giant axons of the squid. These axons are isolated essentially free from small fibers and connective tissue, and pure samples of axoplasm may be obtained by extru- sion of the axon. Incorporation of amino acids into axonal protein has recently been reported using systems from mammals'0 and fish."I Materials and Methods.-Giant axons of Loligo pealii were dissected and freed from small fibers: they were tied at both ends. Incubations were carried out at 18-20° in sea water previously filtered through Millipore which contained 5 mM Tris pH 7.8 and 10 Muc/ml of a mixture of 15 C'4-labeled amino acids (New England Nuclear Co., Boston, Mass.).
    [Show full text]
  • (Caspr) and Contactin Form a Complex That Is Targeted to the Paranodal Junctions During Myelination
    The Journal of Neuroscience, November 15, 2000, 20(22):8354–8364 Contactin-Associated Protein (Caspr) and Contactin Form a Complex That Is Targeted to the Paranodal Junctions during Myelination Jose C. Rios,1 Carmen V. Melendez-Vasquez,1 Steven Einheber,1 Marc Lustig,2 Martin Grumet,2 John Hemperly,5 Elior Peles,6 and James L. Salzer1,3,4 Departments of 1Cell Biology, 2Pharmacology, 3Neurology, and the 4Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, 5BD Technologies, Research Triangle Park, North Carolina 27709, and 6Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel Specialized paranodal junctions form between the axon and the associated specifically with Caspr in the paranodes, whereas a closely apposed paranodal loops of myelinating glia. They are higher-molecular-weight form of contactin, not associated with interposed between sodium channels at the nodes of Ranvier Caspr, is present in central nodes of Ranvier. These results and potassium channels in the juxtaparanodal regions; their suggest that the targeting of contactin to different axonal do- precise function and molecular composition have been elusive. mains may be determined, in part, via its association with Caspr. We previously reported that Caspr (contactin-associated protein) Treatment of myelinating cocultures of Schwann cells and neu- is a major axonal constituent of these junctions (Einheber et al., rons with RPTP␤–Fc, a soluble construct containing the carbonic 1997). We now report that contactin colocalizes and forms a cis anhydrase domain of the receptor protein tyrosine phosphatase complex with Caspr in the paranodes and juxtamesaxon.
    [Show full text]
  • 11 Introduction to the Nervous System and Nervous Tissue
    11 Introduction to the Nervous System and Nervous Tissue ou can’t turn on the television or radio, much less go online, without seeing some- 11.1 Overview of the Nervous thing to remind you of the nervous system. From advertisements for medications System 381 Yto treat depression and other psychiatric conditions to stories about celebrities and 11.2 Nervous Tissue 384 their battles with illegal drugs, information about the nervous system is everywhere in 11.3 Electrophysiology our popular culture. And there is good reason for this—the nervous system controls our of Neurons 393 perception and experience of the world. In addition, it directs voluntary movement, and 11.4 Neuronal Synapses 406 is the seat of our consciousness, personality, and learning and memory. Along with the 11.5 Neurotransmitters 413 endocrine system, the nervous system regulates many aspects of homeostasis, including 11.6 Functional Groups respiratory rate, blood pressure, body temperature, the sleep/wake cycle, and blood pH. of Neurons 417 In this chapter we introduce the multitasking nervous system and its basic functions and divisions. We then examine the structure and physiology of the main tissue of the nervous system: nervous tissue. As you read, notice that many of the same principles you discovered in the muscle tissue chapter (see Chapter 10) apply here as well. MODULE 11.1 Overview of the Nervous System Learning Outcomes 1. Describe the major functions of the nervous system. 2. Describe the structures and basic functions of each organ of the central and peripheral nervous systems. 3. Explain the major differences between the two functional divisions of the peripheral nervous system.
    [Show full text]
  • Chapter 22 – Neuromuscular Physiology and Pharmacology J. A. Jeevendra Martyn
    Chapter 22 – Neuromuscular Physiology and Pharmacology J. A. Jeevendra Martyn The physiology of neuromuscular transmission could be analyzed and understood at the most simple level by using the classic model of nerve signaling to muscle through the acetylcholine receptor. The mammalian neuromuscular junction is the prototypical and most extensively studied synapse. Research has provided more detailed information on the processes that, within the classic scheme, can modify neurotransmission and response to drugs. One example of this is the role of qualitative or quantitative changes in acetylcholine receptors modifying neurotransmission and response to drugs.[1][2] In myasthenia gravis, for example, the decrease in acetylcholine receptors results in decreased efficiency of neurotransmission (and therefore muscle weakness)[3] and altered sensitivity to neuromuscular relaxants.[1][2] Another example is the importance of nerve-related (prejunctional) changes that alter neurotransmission and response to drugs.[1][4] At still another level is the evidence that muscle relaxants act in ways that are not encompassed by the classic scheme of unitary site of action. The observation that muscle relaxants can have prejunctional effects[5] or that some nondepolarizers can also have agonist-like stimulatory actions on the receptor[6] while others have effects not explainable by purely postsynaptic events[7] has provided new insights into some previously unexplained observations. Although this multifaceted action-response scheme makes the physiology and
    [Show full text]
  • Neuromuscular Junctions in the Body Wall Muscles of the Earthworm, Lumbricus Terrestris Linn
    J. Cell Set, 7, 263-271 (1970) 263 Printed in Great Britain NEUROMUSCULAR JUNCTIONS IN THE BODY WALL MUSCLES OF THE EARTHWORM, LUMBRICUS TERRESTRIS LINN. P. J. MILL AND M. F. KNAPP Department of Zoology, University of Leeds, England SUMMARY The fine structure of the neuromuscular junctions in the body wall muscles of the earthworm 13 described. The segmental nerves send branches into the muscle layers. Axons in the nerve branches contain numerous synaptic vesicles and contact is established between these axons and muscle fibres or muscle tails; the latter may extend for a considerable distance from the muscle fibre. The cleft between the axolemma and sarcolemma is 85-120 nm wide and con- tains basement membrane material. At intervals small aggregations of electron-dense material are attached to the axonal membrane and synaptic vesicles are associated with these. The sarcolemma bears rather larger masses of dense material and is also specialized extracellularly. INTRODUCTION The earthworm's body wall muscles are innervated by the segmental nerves. There are about 300 motor fibres in the segmental nerves of a typical segment of the earth- worm Pherettma communissima (Ogawa, 1939); these innervate at least 120000 muscle fibres. The axons give off many branches to the muscles and their endings are den- dritic in form in fully grown worms but bud-like in young worms. According to Retzius (1892 a), finely branching motor fibres ramify in the muscles of Lumbricus, terminating as free endings which are like knotted threads in appearance. His figures indicate both multiterminal and polyneuronal innervation. Smallwood (1926) in an investigation of Lumbricus terrestris, noted that in addition to fine branching nerve fibres with knob-like endings, which he considered to be sensory, there is another type of ending characterized by a cluster of branches, but also with knob-like terminals; he thought that these were motor in function.
    [Show full text]
  • Glial M6B Stabilizes the Axonal Membrane at Peripheral Nodes of Ranvier
    Received: 9 August 2017 | Revised: 6 December 2017 | Accepted: 11 December 2017 DOI: 10.1002/glia.23285 RESEARCH ARTICLE Glial M6B stabilizes the axonal membrane at peripheral nodes of Ranvier Marie L Bang1 | Anya Vainshtein1 | Hyun-Jeong Yang1 | Yael Eshed-Eisenbach1 | Jerome Devaux2 | Hauke B Werner3 | Elior Peles1 1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Abstract Israel Glycoprotein M6B and the closely related proteolipid protein regulate oligodendrocyte myelination 2Aix-Marseille University, CNRS, CRN2M- in the central nervous system, but their role in the peripheral nervous system is less clear. Here we UMR 7286, Marseille, France report that M6B is located at nodes of Ranvier in peripheral nerves where it stabilizes the nodal 3 Department of Neurogenetics, Max Planck axolemma. We show that M6B is co-localized and associates with gliomedin at Schwann cell Institute of Experimental Medicine, microvilli that are attached to the nodes. Developmental analysis of sciatic nerves, as well as of Goettingen, Germany myelinating Schwann cells/dorsal root ganglion neurons cultures, revealed that M6B is already Correspondence present at heminodes, which are considered the precursors of mature nodes of Ranvier. However, Elior Peles, Department of Molecular Cell in contrast to gliomedin, which accumulates at heminodes with or prior to Na1 channels, we often Biology, Weizmann Institute of Science, detected Na1 channel clusters at heminodes without any associated M6B, indicating that it is not Rehovot, 76100, Israel. E-mail: [email protected] required for initial channel clustering. Consistently, nodal cell adhesion molecules (NF186, NrCAM), ion channels (Nav1.2 and Kv7.2), cytoskeletal proteins (AnkG and bIV spectrin), and microvilli com- Funding information ponents (pERM, syndecan3, gliomedin), are all present at both heminodes and mature nodes of NIH, Grant Number: R01NS097428; Israel Science Foundation; Dr.
    [Show full text]
  • Synapse Transmission
    Synapse Transmission There are two types of synapses found in your body: electrical and chemical. Electrical synapses allow the direct passage of ions and signaling molecules from cell to cell. In contrast, chemical synapses do not pass the signal directly from the presynaptic cell to the postsynaptic cell. In a chemical synapse, an action potential in the presynaptic neuron leads to the release of a chemical messenger called aneurotransmitter. The neurotransmitter then diffuses across the synapse and binds to receptors on the postsynaptic cell. Binding of the neurotransmitter leads to the production of an electrical signal in the postsynaptic cell. Why does the body have two types of synapses? Each type of synapse has functional advantages and disadvantages. An electrical synapse passes the signal very quickly, which allows groups of cells to act in unison. A chemical synapse takes much longer to transmit the signal from one cell to the next; however, chemical synapses allow neurons to integrate information from multiple presynaptic neurons, determining whether or not the postsynaptic cell will continue to propagate the signal. Neurons respond differently based on information transmitted by multiple chemical synapses. Let’s take a closer look at the structure and function of each type of synapse. Electrical synapses transmit action potentials via the direct flow of electrical current at gap junctions. Gap junctions are formed when two adjacent cells have transmembrane pores that align. The membranes of the two cells are linked together and the aligned pores form a passage between the cells. Consequently, several types of molecules and ions are allowed to pass between the cells.
    [Show full text]
  • Components of the Plasma Membrane of Growing Axons. I. Size And
    Components of the Plasma Membrane of Growing Axons. I . Size and Distribution of Intramembrane Particles ROCHELLE K . SMALL and KARL H . PFENNINGER Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York 10032. Dr. Small's present address is Department of Pathology (Immunology), Yale University, School of Medicine, New Haven, Connecticut 06510. ABSTRACT The plasmalemma of mature and growing olfactory axons of the bullfrog has been studied by freeze-fracture . Intramembrane particles (IMPs) of mature olfactory axons are found to be uniformly distributed along the shaft. However, during growth, a decreasing gradient of IMP density is evident along the somatofugal axis. The size histograms of axolemmal IMPs from different segments of growing nerve reveal regional differences in the particle composi- tion . The distribution of each individual size class of particles along the growing nerve forms a decreasing gradient in the somatofugal direction ; the slope of these gradients varies directly with particle diameter. These size-dependent density gradients are consistent with a process of lateral diffusion of membrane components that are inserted proximally into the plasma membrane. The membrane composition of the growth cone, however, appears to be inde- pendent of these diffusion gradients ; it displays a mosaic pattern of discrete domains of high and low particle densities . The relative IMP profiles of these growth cone regions are similar to one another but contain higher densities of large IMPs than the neighboring axonal shaft. The shifting distributions of intramembrane particles that characterize the sprouting neuron give new insights into cellular processes that may underlie the establishment of the functional polarity of the neuron and into the dynamics of axolemmal maturation.
    [Show full text]
  • Effect of Alpha-Latrotoxin on the Frog Neuromuscular Junction at Low
    Journal of Physiology (1988), 402, pp. 195-217 195 With 4 plate8 and 5 text-figures Printed in Great Britain EFFECT OF ae-LATROTOXIN ON THE FROG NEUROMUSCULAR JUNCTION AT LOW TEMPERATURE BY B. CECCARELLI, W. P. HURLBUT* AND N. IEZZI From the Department of Medical Pharmacology, CNR Center of Cytopharmacology and Center for the Study of Peripheral Neuropathies and Neuromuscular Diseases, Via Vanvitelli 32, 20129 Milano, Italy, and the Rockefeller University*, 1230 York Avenue, New York, NY 10021, U.S.A. (Received 13 July 1987) SUMMARY 1. a-Latrotoxin (a-LTx) was applied to frog cutaneus pectoris muscles bathed at 1-3 °C in either Ringer solution, Ca2"-free Ringer solution with 1 mM-EGTA and 4 mM-Mg2+ or Ringer solution plus 4 mM-Mg2+, and its effects on miniature end-plate potential (MEPP) frequency, nerve terminal ultrastructure and uptake of horse- radish peroxidase (HRP) were studied. 2. Large concentrations (2 ,ug/ml) of a-LTx increased MEPP rates to levels above 100/s at all junctions, but the time course of the increases depended upon the divalent cation content of the bathing solution. However, similar numbers ofMEPPs (0-3-407 x 106) were recorded at all junctions during 2 h of secretion. 3. Nerve terminals exposed to a-LTx for 2 h lost 60-75 % oftheir synaptic vesicles and were swollen; their presynaptic membranes were deeply infolded and they often contained many large vesicular structures. Terminals in Ringer solution retained the largest number of synaptic vesicles; terminals in Ringer solution plus Mg2+ swelled the least and contained the largest number of coated vesicles.
    [Show full text]