Single-fiber Studies Research Articles

Light diffraction studies of single muscle fibers as a function of fiber rotation

Light diffraction patterns from single glycerinated frog semitendinosus muscle fibers were examined photographically and photoelectrically as a function of diffraction angle and fiber rotation. The total intensity diffraction pattern indicates that the order maxima change both position and intensity periodically as a function of rotation angle. The total diffracted light, light diffracted above and below the zero-order plane, and light diffracted into individual orders gives information about the fiber's longitudinal and rotational structure and its noncylindrical symmetry.

The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit.

Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed.

Perspectives and future trends in cellular electrophysiology: Implications for the clinician

As a result of single fiber electrophysiologic studies, the clinical approach to the electrical behavior of the heart has improved. Three areas are examined: 1) the electrocardiographic waveform, 2) normal and abnormal cardiac rhythms, and 3) the mechanism of action of antiarrhythmic drugs. In each area, the results of single fiber studies have provided a conceptual framework for diagnostic and therapeutic decisions. These studies have also enabled investigators to test hypotheses formulated from clinical observations. It may be only a slight exaggeration to attribute many of our recent advances in each of the three areas to the development and use of the microelectrode.

Peripheral neuropathy associated with monoclonal gammopathy. Studies of intraneural injections of monoclonal immunoglobulin sera.

A causal relationship between paraproteinemia and neuropathies has been suggested. We studied three patients with chronic sensorimotor polyneuropathy associated with plasma cell dyscrasia and monoclonal gammopathies (IgGK, IgMK, IgA lambda). Sural nerve biopsies showed mild (2 cases) to moderate loss of myelinated fibers (1 case). Teased single fiber studies showed segmental demyelination-remyelination in two patients. Direct immunofluorescence demonstrated immune deposits of the myelin sheath of the same specificity as the serum paraprotein, IgGK (1 of 3 cases). Treatment with prednisone, melphalan or chlorambucil, and plasmapheresis resulted in remission (1 case), partial improvement (1 case), or had no effect (1 case), although reduction of monoclonal immunoglobulin occurred in all. To investigate the role the paraproteins might play in the pathogenesis of the neuropathy, patients' serum was injected intraneurally into rat sciatic nerves. None of the animals developed weakness, slowing of in vitro conduction of sciatic nerve, or significant evidence of demyelination by light- or electron-microscopy or teased single fiber studies 48 hours postinjection. Similar injections of rabbit serum with experimental allergic neuritis (EAN) produced focal segmental demyelination. Our studies employing an in vivo bioassay technique failed to establish antimyelin activity of monoclonal immunoglobulin sera.

Rate-versus-intensity functions and related AP responses in normal and pathological guinea pig and human cochleas.

Cochlear fiber discharge rate-versus-intensity functions, across frequency, have been measured in pathological guinea pig cochleas (ototoxic antibiotic poisoning) and compared with the normal animal. The frequency dependence of the slopes of these functions is reduced in cochlear pathology which results in minimum threshold elevations of more than 50 dB, i.e., there is a reduction in this frequency dependent nonlinearity. The rate functions at characteristic frequency (CF) become abnormally steep (e.g., 4--5 spikes/s/dB compared with a normal 1--2 spikes/s/dB), and comparable to those of the low-frequency tail region of normal cochlear fibers. The CF dynamic range is reduced from 30--40 to 10--15 dB in cochlear pathology. The fiber study has been confirmed by (and has confirmed) a method of indirect measurement of rate functions from AP suppression-versus-intensity functions using a pure-tone forward masking paradigm [Abbas and Gorga, J. Acoust. Soc. Am. 69, 492--499 (1981)]. This method has been used in normal and pathological guinea pigs, and the results parallel the single fiber study. In addition, AP suppression functions, across frequency, have been obtained in human subjects with (near) normal hearing thresholds, and in patients with sensorineural hearing loss of cochlear origin, during transtympanic electrocochleography. The AP suppression curves in pathology indicate, as for the animal studies, a loss of the frequency dependency of the rate function slopes, and predict steep rate functions at CF (and thus reduced dynamic range) in cochlear deafness. The findings are related to loudness recruitment.

Quasi-elastic light-scattering studies of single skeletal muscle fibers

Measurements were made of the intensity autocorrelation function, g(2)[tau], of light scattered from intact frog muscle fibers. During the tension plateau of an isometric tenanus, scattered field statistics were approximately Gaussian and intensity fluctuations were quasi-stationary. The half time, tau 1/2, for the decay of g(2)[tau] was typically 70 ms at a scattering angle of 30 degrees. The decay rate, 1/tau 1/2, of g(2)[tau] varied roughly linearly with the projection of the scattering vector on the fiber axis. 1/tau 1/2 was greater during the tension creep phase of tetani of highly stretched fibers, but was roughly independent of sarcomere length during the tension plateau. g(2)[tau] measured during rest or on diffraction pattern maxima during isometric contraction were flat with low amplitudes. These results are consistent with a model of a 200-mu m segment of an isometrically contracting fiber in which scattering material possesses relative axial velocities of 1-2 mu m/s accompanied by relative axial displacements greater than 0.1 mu m. The slow (1-2 mu m/s) motion of one portion of the fiber relative to another observed under the microscope (500X) during isometric contraction is consistent with the light-scattering results. Structural fluctuations on the scale of the myofibrillar sarcomere which may arise from asynchronous cycling of cross-bridges must involve relative axial velocities less than 3 mu m/s or relative axial displacements less than 0.05 mu m.

Gamma-radiation-induced grafting onto wool—I: Fundamental studies on loose wool

Radiation-induced grafting studies have been carried out on loose wool fibres. Different vinyl monomers were used and they were grafted in different solvents which were selected on the basis of their swelling efficiency and solubility parameters. The treatments were performed once with and once without the addition of water. The presence of water caused the polymer uptake to increase considerably. Formic acid/methanol and methanol accelerate the grafting process best, since they have the highest hydrogen-bond interaction efficiency. The moisture uptake of grafted wool decreases. X-ray and differential scanning calorimetry tests show unambiguously that grafting occurs in different morphological areas, depending on the type of polymer. The single fibre studies served as basis for analogous tests on wool fabrics (Part II).

Single‐fiber electromyography in myasthenia gravis

One-hundred-sixty single-fiber EMG studies of the extensor digitorum communis muscle were performed on 127 patients with myasthenia gravis; 131 demonstrated defective neuromuscular transmission. Jitter determinations in the biceps, deltoid or frontalis muscles increased the diagnostic yield significantly. Evoked-potential EMG studies were abnormal in less than 50 percent of patients in whom they were performed. The most sensitive criterion of abnormality was the percentage of fibers with increased jitter; the sensitivity of the test was enhanced, however, if the mean jitter of the tested muscle was also used as a criterion of abnormality. Since increased jitter may also be seen in primary muscle and nerve disease, these disorders must be excluded by other means before diagnosing myasthenia gravis on the basis of the single-fiber studies.

Peripheral nervous system pathology in relapsing experimental allergic encephalomyelitis.

A recurrent type of primary demyelination was found in the anterior roots and dorsal root ganglia of strain 13 guinea-pigs with relapsing experimental allergic encephalomyelitis. Single nerve fibre studies revealed a predominant nodal--paranodal distribution of the destruction of myelin in these nerves. Damage of the Schwann cell--axolemmal junction was found in the majority of the abnormal nodes of Ranvier. This was accompanied by the formation of supernumerary adaxonal Schwann cell processes which further altered the normal myelinating cell--axon relationship. It is concluded that variations in antigenic composition may play a role in the selective involvement of the anterior roots. The pathogenesis of the observed nodal changes is discussed.

Molecular mechanisms of nerve block by local anesthetics

Local anesthetics block nerve conduction by preventing the increase in membrane permeability to sodium ions that normally leads to a nerve impulse. Among anesthetics containing tertiary amine groups, the cationic, protonated form appears to be more active than the neutral form. However, the neutral forms, as well as uncharged molecules like benzocaine and the aliphatic alcohols, also depress sodium permeability. Studies of single myelinated nerves and squid axons show no direct interaction between calcium ions and local anesthetics, thus disproving theories based on competition between these two agents. Likewise, hypotheses attributing local anesthesia to changes in electrical potentials at the membrane-water interface are disproven by the demonstrated potencies of electrically uncharged anesthetics. Hypotheses that propose that local anesthetics act by expanding the nerve membrane and causing a change in protein conformation that blocks sodium permeability are vague in conception and difficult to test experimentally. Evidence from voltage-clamp studies of single nerve fibers indicates that anesthetic molecules interact with the sodium channels directly, from the inner side of the nerve membrane. Anesthetics bind within sodium channels which have opened during membrane depolarization, preventing the normal sodium ion flux. Anesthetic molecules can dissociate from open channels, but not from channels that remain closed when the nerve is kept at rest. The gating properties that regulate the opening and closing of sodium channels are reversibly modified during anesthesia. Specifically, the inactivation function responds more slowly and requires more negative membrane potential changes to reach the same values as in unanesthetized nerves. A second, slow inactivation is observed following external application of tertiary amine anesthetics. The selective binding of anesthetics to open sodium channels provides a simple explanation for Wedenski inhibition, in which the block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics...

The peroneal muscular atrophy syndrome: Clinical, genetic, electrophysiological and nerve biopsy studies part 2. Observations on pathological changes in sural nerve biopsies

The light- and electron-microscopic, single teased nerve fibre and morphometric studies of a series of 17 sural nerve biopsies from patients with peroneal muscular atrophy are presented. The cases are divided into the following groups according to the criteria of Davis, Bradley and Madrid (1977): Hypertrophic Neuropathy Group; Intermediate Group; Neuronal Sensorimotor Group; Neuronal Motor Group. The Hypertrophic Neuropathy Group had nerve hypertrophy and marked segmental demyelination with onion bulb formation. The Intermediate Group also had segmental demyelination and onion bulb formation, but nerve hypertrophy was not seen, and axonal degeneration and regeneration were prominent. The Neuronal Sensorimotor Group cases were all sporadic, and showed some onion bulbs, paranodal demyelination and evidence of axonal degeneration and regeneration. The sensory nerve biopsy in the Neuronal Motor Group showed no major abnormality apart from some cluster formation indicating axonal regeneration. The data tend to support the classification of peroneal muscular atrophy proposed by Davis et al. (1977), though there was overlap between the groups in individual pathological parameters.

Molecular mechanisms of nerve block by local anesthetics.

Local anesthetics block nerve conduction by preventing the increase in membrane permeability to sodium ions that normally leads to a nerve impulse. Among anesthetics containing tertiary amine groups, the cationic, protonated form appears to be more active than the neutral form. However, the neutral forms, as well as uncharged molecules like benzocaine and the aliphatic alcohols, also depress sodium permeability. Studies of single myelinated nerves and squid axons show no direct interaction between calcium ions and local anesthetics, thus disproving theories based on competition between these two agents. Likewise, hypotheses attributing local anesthesia to changes in electrical potentials at the membrane-water interface are disproven by the demonstrated potencies of electrically uncharged anesthetics. Hypotheses that propose that local anesthetics act by expanding the nerve membrane and causing a change in protein conformation that blocks sodium permeability are vague in conception and difficult to test experimentally. Evidence from voltage-clamp studies of single nerve fibers indicates that anesthetic molecules interact with the sodium channels directly, from the inner side of the nerve membrane. Anesthetics bind within sodium channels which have opened during membrane depolarization, preventing the normal sodium ion flux. Anesthetic molecules can dissociate from open channels, but not from channels that remain closed when the nerve is kept at rest. The "gating" properties that regulate the opening and closing of sodium channels are reversibly modified during anesthesia. Specifically, the inactivation function responds more slowly and requires more negative membrane potential changes to reach the same values as in unanesthetized nerves. A second, slow inactivation is observed following external application of tertiary amine anesthetics. The selective binding of anesthetics to open sodium channels provides a simple explanation for Wedenski inhibition, in which the block increases with the frequency of nerve impulses. When impulses occur at higher frequencies more sodium channels are open over a period of time comparable to the time necessary for the anesthetic binding reaction, thus more channels are blocked. In addition the changes of the inactivation function result in a longer refractory period and, thus, a decrease of impulse height at higher frequencies. Charged anesthetic molecules may bind in the pore of the sodium channel. Their binding can be modulated by the electrical field in the membrane. The channel has a higher affinity for larger anesthetic molecules, but this may result from their greater hydrophobicity as well as from their size. The binding site favors molecules that contain more polar linkages between the amine group and the aromatic residue. Binding of amine anesthetics is weakly stereospecific and, surprisingly, shows no absolute requirement for the terminal alkyl ammonium moiety present in most local anesthetics...

Low Angle Electron Scattering from Carbonized Polymer Fibres

MANY observations have been made on carbon or “graphite” fibres by the technique of small angle X-ray scattering1–3. Valuable as these observations are for the investigation of mean scattering parameters from a bundle of fibres they cannot normally be made on single fibres, nor can they easily be correlated with microstructural features in the fibre. For these reasons the technique of low angle electron scattering, carried out in an electron microscope, was expected to be more useful for single fibre studies.

Physiological correlates of auditory stimulus periodicity.

Microelectrode studies of single auditory nerve fibers provide information on physiological mechanisms postulated in the two classical theories of pitch perception. The place principle is exemplified by the threshold vs. frequency or tuning curve for a fiber which typically exhibits maximum sensitivity to a narrow band of frequencies. Computer-controlled stimulus presentation has permitted systematic exploration of the supra – threshold response area throughout the entire domain of effective frequencies and SPL's. These studies demonstrate that the assignment of a single characteristic frequency constitutes an inadequate description of the frequency selectivity of a fiber since the frequency of lowest threshold may be appreciably different from the frequency which causes maximal discharge at higher SPL's. In general, the complexity of the response areas is difficult to reconcile with the simplistic concept that each fiber can be associated with a specific pitch.The Volley theory predicts that stimulus per...

Synaptic inputs to cells in the medial vestibular nucleus.

Synaptic inputs to cells in the medial vestibular nucleus.V J Wilson, R M Wylie, and L A MarcoV J Wilson, R M Wylie, and L A MarcoPublished Online:01 Mar 1968https://doi.org/10.1152/jn.1968.31.2.176MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByResponses of non-eye-movement central vestibular neurons to sinusoidal yaw rotation in compensated macaques after unilateral semicircular canal pluggingShawn D. Newlands, Min Wei, David Morgan, and Hongge Luan14 October 2016 | Journal of Neurophysiology, Vol. 116, No. 4Central projections of the vestibular nerve: a review and single fiber study in the Mongolian gerbilBrain Research Bulletin, Vol. 60, No. 5-6Synaptic input-induced increase in intraneuronal Ca2+ in the medial vestibular nucleus of young ratsNeuroscience Research, Vol. 21, No. 1Unitary correlates of linguo-pharyngeal events in a dyskinetic rat modelComparative Biochemistry and Physiology Part C: Comparative Pharmacology, Vol. 99, No. 3Compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbilExperimental Brain Research, Vol. 82, No. 2Compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbilExperimental Brain Research, Vol. 82, No. 2Tilt Responses of Semicircular Canal Primary Afferents11 December 2016 | Otolaryngology-Head and Neck Surgery, Vol. 90, No. 1Functional organization of the superior vestibular nucleus of the squirrel monkeyBrain Research, Vol. 132, No. 1A new long spinal projection from the vestibular nuclei in the catBrain Research, Vol. 122, No. 2Characteristics of responses of medial brain stem neurons to horizontal head angular acceleration and electrical stimulation of the labyrinth in the catBrain Research, Vol. 120, No. 3Crossed sacculo-ocular pathway via the deiters' nucleus in catsBrain Research Bulletin, Vol. 2, No. 1Horizontal vestibular nystagmus. I. Identification of medial vestibular neuronesExperimental Brain Research, Vol. 26, No. 4Horizontal vestibular nystagmus. II. Activity patterns of medial vestibular neurones during nystagmusExperimental Brain Research, Vol. 26, No. 4Brain stem and cerebellar lesions in female rats. I. Tests of posture and movementBrain Research, Vol. 106, No. 1Functions of extrapyramidal systems in motor controlPharmacology & Therapeutics. Part B: General and Systematic Pharmacology, Vol. 1, No. 4Neural Activity in the Vestibular Nuclei of the Cat28 June 2016 | Annals of Otology, Rhinology & Laryngology, Vol. 82, No. 6Neural Activity in the Vestibular Nuclei of the Cat4 December 2016 | Annals of Otology, Rhinology & Laryngology, Vol. 82, No. 9_supplSemicircular canal input to pigeon vestibulocerebellumBrain Research, Vol. 45, No. 1Projections des creˆstes ampullaires et de l'utricule dans les noyaux vestibulaires primaires.étude microphysiologique et corrélations anatomo-fonctionnellesBrain Research, Vol. 44, No. 2Commissural projection from the nuclei of termination of the VIIIth cranial nerve in the toadBrain Research, Vol. 42, No. 1The vestibular nuclei and spinal motor activityJournal of Psychiatric Research, Vol. 8, No. 3-4Vestibular nerve activation of a brain stem cholinergic system influencing the spinal cordNeuropharmacology, Vol. 10, No. 4Organization of vestibulo-oculomotor projections in the catBrain Research, Vol. 20, No. 2Bilateral connections between labyrinths and neck motoneuronsBrain Research, Vol. 13, No. 3Monosynaptic inhibition of neck motoneurons by fibers originating in the brain stemBrain Research, Vol. 11, No. 3 More from this issue > Volume 31Issue 2March 1968Pages 176-85 https://doi.org/10.1152/jn.1968.31.2.176PubMed5687381History Published online 1 March 1968 Published in print 1 March 1968 Metrics

Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway.

Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway.

Disturbances of Rhythmicity and Conduction.

s1 April 1962Disturbances of Rhythmicity and Conduction.B. F. Hoffman, M.D.B. F. Hoffman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-667_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptElectrocardiographic records are employed to show the type of disturbance of rhythm or conduction. Such records often indicate the site of ectopic pacemakers, the site of disturbed conduction, or both. However, to obtain information on the mechanism responsible for altered rhythmicity or detailed information on the exact localization and mechanism of conduction disturbances, other techniques are necessary. Two which have been employed with some success in recent years are microelectrode studies of single cardiac fibers in isolated preparations and direct records from the specialized conducting system in intact hearts. Results obtained through use of these techniques are described in an... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, N. Y. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 667-668KeywordsElectrocardiographyElectrode recordingHeartLongitudinal studiesPacemakers Issue Published: 1 April 1962 PDF DownloadLoading ...

Physiologic basis of disturbances of cardiac rhythm and conduction

Recent studies of the electrophysiology of cardiac muscle and in particular the fibers of the specialized tissues of the heart have provided information on several physiologic mechanisms which can be responsible for the production of disturbances of rhythm and conduction. Intrinsic rhythmicity is a property of all of the specialized fibers; in some, slow diastolic depolarization is always present, and thus these fibers are latent pacemakers which can and will generate ectopic activity at any time that the frequency of the normal pacemaker is depressed or at any time that their own intrinsic frequency is enchanced. Other fibers may show little evidence of intrinsic rhythmicity under normal conditions but, when influenced by a wide variety of factors (hypoxia, sympathetic activity, stretch, local changes in concentration of K, Ca ++ , pH and others) will develop rapid pacemaker activity. In addition to the property of intrinsic rhythmicity which is present in the specialized fibers, the differences in action potential duration and conduction velocity of these same cells enhances the likelihood of complex arrhythmias. Studies of single fibers must now be supplemented by records from the specialized conducting system of the intact heart during the clinically important arrhythmias to determine the exact manner in which each disturbance of rate and rhythm is brought about.

A Silver-glass Micro-electrode for Use in a Micromanipulator

In an investigation of the neuro-motor mechanism of small blood vessels,1 the author needed to make micro-electrodes for the stimulation of small nerve fibers. The non-polarizable type (micro-salt-bridge), described by Ettisch and Peterfi,2 Taylor,3 Gelfan,4 and Field,5 was not necessary. Various polarizable types described in the literature were found to be inadequate. The platinum-quartz micro-electrode, devised by Taylor3 and used by Pratt and Reid6 and by Steiman7 for the study of single muscle fibers, proved to be expensive, required an oxygen flame to draw, and broke easily. The micro-electrode described by Sen8 may be produced in quantity by the deposition of metallic platinum, gold, or silver on the surface of quartz or glass micro-needles, using Brashear's method for silvering glass or the method of sputtering with a high voltage discharge in a vacuum. Electrodes of this type had to be insulated individually by the application of shellac with a small brush. It was found that the insulation did no...

CEREBELLAR ACTION POTENTIALS IN RESPONSE TO STIMULATION OF VARIOUS AFFERENT CONNECTIONS

CEREBELLAR ACTION POTENTIALS IN RESPONSE TO STIMULATION OF VARIOUS AFFERENT CONNECTIONS