Acetaldehyde affects mammalian neuromuscular transmission without observable postsynaptic effects

1978 ◽  
Vol 56 (6) ◽  
pp. 1063-1066 ◽  
Author(s):  
Peter L. Carlen ◽  
Allan L. Staiman ◽  
William A. Corrigall
Keyword(s):  
Action Potential ◽  
Phrenic Nerve ◽  
Neuromuscular Transmission ◽  
Compound Action Potential ◽  
Base Line ◽  
Muscle Action ◽  
End Plate ◽  
Muscle Action Potential ◽  
Higher Doses ◽  
Compound Action

Acetaldehyde, the first metabolite of ethanol, caused a reversible block of the end-plate potential (EPP) in the rat and mouse phrenic nerve – hemidiaphragm preparation. Decrease and block of the EPP occurred over a bath concentration range from 3 to 25 mM. The phrenic nerve compound action potential was blocked along with the EPP, and this block was not reversed by high bath Ca2+ concentration. The muscle action potential was unaffected even at concentrations up to 50 mM. Over the same concentration range (3–25 mM), miniature end-plate potential (MEPP) frequency sometimes decreased a few minutes after application, and over the ensuing 10–20 min would steadily increase to as much as 11 times the base-line frequency, particularly with higher doses. However, the shape of averaged MEPPs remained unchanged after acetaldehyde application, suggesting that this aldehyde does not have postsynaptic effects.

Development of 4-AP and TEA sensitivities in mammalian myelinated nerve fibers

1988 ◽  
Vol 60 (6) ◽  
pp. 2168-2179 ◽  
Author(s):  
D. L. Eng ◽  
T. R. Gordon ◽  
J. D. Kocsis ◽  
S. G. Waxman
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Compound Action Potential ◽  
Nerve Fibers ◽  
Repetitive Firing ◽  
Base Line ◽  
Channel Blockers ◽  
Myelinated Nerve ◽  
Sucrose Gap ◽  
Compound Action

1. The sensitivities of mammalian myelinated axons to potassium channel blockers was studied over the course of development using in vitro sucrose gap and intra-axonal recording techniques. 2. Application of 4-aminopyridine (4-AP; 1.0 mM) to young nerves led to a delay in return to base line of the sciatic nerve compound action potential and to a postspike positivity (indicative of hyperpolarization) lasting for tens of milliseconds. These effects were very much attenuated during the course of maturation. 3. Tetraethylammonium chloride (TEA; 10 mM) application alone had little effect on the waveform of the compound action potential at any age. However, the 4-AP-induced postspike positivity was blocked by TEA, Ba/+, and Cs+. This block was observed in Ca2+-free electrolyte solutions containing EGTA (1.0 mM). 4. Immature sciatic nerves (approximately 3 wk postnatal) were incubated in a potassium-free electrolyte solution containing 120 mM CsCl for up to 1 h in an attempt to replace internal potassium with cesium. When the nerves were tested in the sucrose gap chamber using solutions containing 3.0 mM CsCl substituted for KCl, the compound action potential was broadened and a prolonged depolarization appeared, but there was no postspike positivity; the CsCl effect was similar to the combined effects of 4-AP and TEA. 5. Intra-axonal recordings were obtained to study the effects of 4-AP and TEA on individual axons. In the presence of 4-AP a single stimulus led to a burst of action potentials followed by a pronounced afterhyperpolarization (AHP) in sensory fibers. The AHP was blocked by TEA. In motor fibers 4-AP application resulted in action potential broadening with no AHP. 6. Repetitive stimulation (200-500 Hz; 100 ms) was followed by a pronounced AHP in both sensory and motor fibers at all ages studied. This activity-elicited AHP was sensitive to TEA at all ages. 7. The results indicate that 4-AP and TEA sensitivity change over the course of development in rat sciatic nerve. The effects of 4-AP are much more pronounced in immature nerves than in mature nerves, suggesting that 4-AP-sensitive channels become masked as they are covered by myelin during maturation. However, the TEA-sensitive channels, demonstrable after repetitive firing, remain accessible to TEA after myelination. These channels therefore may have a nodal representation.

Electrophysiological evaluation of phrenic nerve function in candidates for diaphragm pacing

1980 ◽  
Vol 53 (3) ◽  
pp. 345-354 ◽  
Author(s):  
Richard K. Shaw ◽  
William W. L. Glenn ◽  
James F. Hogan ◽  
Mildred L. Phelps
Keyword(s):  
Action Potential ◽  
Nerve Injury ◽  
Nerve Stimulation ◽  
Phrenic Nerve ◽  
Conduction Time ◽  
Nerve Function ◽  
Muscle Action ◽  
Phrenic Nerve Stimulation ◽  
Diaphragm Pacing ◽  
Muscle Action Potential

✓ The electrophysiological status of phrenic nerve function has been determined by an assessment of the conduction time and diaphragm muscle action potential in patients who were being evaluated as candidates for diaphragm pacing, or who were being studied for suspected phrenic nerve injury or disease. The conduction time and muscle action potential were evoked by transcutaneous phrenic nerve stimulation or by stimulation with a permanently implanted diaphragm pacemaker. In normal volunteers, the conduction time was found to be 8.40 msec ± 0.78 msec (SD). Transcutaneous phrenic nerve stimulation was successful in predicting phrenic nerve viability in 116 of 120 nerves studied. The four false negatives were due to technical difficulty in locating the nerves in obese or uncooperative subjects. In patients who were selected for implantation of a diaphragm pacemaker, a conduction time that was prolonged (10 to 14 msec) preoperatively did not preclude successful diaphragm pacing. Postoperatively, a prolonged (> 10 msec) conduction time was associated with severe systemic disease or local nerve injury caused by trauma or infection. The elucidation of phrenic nerve function by such electrophysiological studies serves as a valuable adjunct to the selection and management of patients undergoing diaphragm pacing.

scholarly journals UNMEDULLATED FIBERS ORIGINATING IN DORSAL ROOT GANGLIA

1950 ◽  
Vol 33 (6) ◽  
pp. 651-690 ◽  
Author(s):  
Herbert S. Gasser
Keyword(s):  
Action Potential ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
High Sensitivity ◽  
Compound Action Potential ◽  
Sympathetic Ganglia ◽  
Base Line ◽  
Positive Potential ◽  
Histological Data ◽  
Compound Action

The compound action potential of the unmedullated fibers arising from dorsal root ganglia, as recorded in cat skin nerves after conduction of simultaneously initiated impulses, shows among its components a temporal dispersion corresponding to velocities between 2.3 and 0.7 M.P.S. The maximum representation of the component velocities is at about 1.2 M.P.S. On both sides of the maximum the representation falls off irregularly, in such a way that groupings in the distribution produce in the action potential a configuration in which successive features appear always in the same positions at a given conduction distance. Through this demonstration of a characteristic configuration the system of the unmedullated fibers is brought into analogy with that of the medullated fibers. The unmedullated fibers originating in the dorsal root ganglia have distinctive physiological properties, among which is a large positive potential which reaches its maximum immediately after the spike and decrements to half relaxation in about 50 msec., at 37°C. The positive phases of the unit potentials in the compound action potential, owing to their duration, sum to a much greater extent than the temporally dispersed spikes; and, since they have sizes such that one equivalent to 25 per cent of the spike height would not be at the limit, in the summation process the major portion of the compound action potential is caused to be written at a potential level positive to the starting base line. The position of the spikes in the sequence can be seen in the analyses in Section III. The course of the activity in unit fibers is subject to variation in ways affecting the positive potential. Preliminary descriptions, based on orienting experiments, of how these variations are conditioned are given in Section I. Two of the findings are particularly noteworthy. One is the high sensitivity of the dimensions of the postspike positivity to temperature in the range of temperatures at which skin nerves may be expected to function, even when the environmental temperatures of an animal are moderate. The other is the high sensitivity to conditioning by previous activity. The positivity is first decreased, then replaced by a negative potential of similar duration. Reasons have been given why it is inadvisable at the present time to call the postspike potential an after-potential. A comparison has been made of the properties of the unmedullated fibers arising from dorsal root ganglia with those of fibers arising from sympathetic ganglia. The differences are so great that, in the interest of precision in designation, a division of the C group of fibers into two subgroups is indicated. It is suggested that the two subgroups be named respectively d.r.C and s.C. Measurements have been made of the diameters of the d.r.C fibers in a saphenous nerve stained with silver. Graphs showing the number of fibers at each diameter are presented in Section II. In Section III there are shown constructions, from histological data, of the action potential as it would appear, after 3 cm. of conduction, with the correlation between diameter and velocity in strict linearity. The degree of fit between the constructed and recorded potentials can be seen in Fig. 18.

The Impulse-Blocking Concentrations of Anesthetics, Alcohols, Anticonvulsants, Barbiturates, and Narcotics on Phrenic and Sciatic Nerves

1974 ◽  
Vol 52 (3) ◽  
pp. 535-550 ◽  
Author(s):  
A. Staiman ◽  
P. Seeman
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Phrenic Nerve ◽  
Partition Coefficients ◽  
Compound Action Potential ◽  
Tertiary Amines ◽  
Response Curves ◽  
Acidic Drugs ◽  
Sciatic Nerves ◽  
Compound Action

(1) The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat. Skou's second method for equilibrium blockade was used, and complete dose–response curves were obtained on the height of the compound action potential.(2) Uncharged drugs (alcohols, urethane) and acidic drugs (barbiturates, diphenylhydantoin) caused half blockade of the phrenic nerve (11 μm diameter fibers) at concentrations about 25–35% of those causing half blockade of sciatic nerve (16 μm fibers).(3) Tertiary amines (procaine, spirosuccinimide enantiomers, chlorpromazine, haloperidol, trifluperidol, methadone, and naloxone) produced half blockade of the phrenic nerve at concentrations about 10% of those producing half blockade of the sciatic nerve. Frog and rat sciatic C50% block values (i.e. the drug concentration that reduced the compound action potential by 50%) were the same.(4) The phrenic C50% block value for tetrodotoxin was 7.1 times higher than that for the sciatic nerve.(5) The phrenic C50% blockvalues of the neutral and acidic drugs (together as a group) correlated inversely with the membrane/buffer partition coefficients of the drugs, in accordance with the classical Meyer–Overton rule of anesthesia. The phrenic C50% block values for the tertiary amines also correlated inversely with the membrane/buffer partition coefficients. Tetrodotoxin did not fit on these two correlations, and appeared to fall into a category of its own.(6) It was concluded that, whether comparing different nerves or the same nerve at different stages of growth, smaller myelinated fibers required lower nerve-blocking concentrations of drugs.

Laryngeal Reinnervation Using the Split-Phrenic Nerve-Graft Procedure

1980 ◽  
Vol 88 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Roger L. Crumley ◽  
Karl Horn ◽  
David Clendenning
Keyword(s):  
Action Potential ◽  
Vocal Cord ◽  
Phrenic Nerve ◽  
Operative Procedure ◽  
Compound Action Potential ◽  
Nerve Graft ◽  
Fluoroscopic Examination ◽  
Laryngeal Reinnervation ◽  
Compound Action

A new operative procedure for reinnervation of the paralyzed larynx is described. Initial successes in a series of animals have shown that use of the split-phrenic nerve-graft procedure results in functional abduction of the paralyzed vocal cord, while preserving innervation to the diaphragm. Electromyography, microlaryngoscopic movies, chest fluoroscopic examination, and nerve compound action potential recordings were all used to document these findings. This procedure appears to have several advantages over the neuromuscular pedicle operation described by Tucker.

Calcium Reversal of Nerve Blockade by Alcohols, Anesthetics, Tranquilizers, and Barbiturates

1974 ◽  
Vol 52 (3) ◽  
pp. 526-534 ◽  
Author(s):  
P. Seeman ◽  
S. S. Chen ◽  
M. Chau-Wong ◽  
A. Staiman
Keyword(s):  
Action Potential ◽  
Benzyl Alcohol ◽  
Phrenic Nerve ◽  
Binding Sites ◽  
Compound Action Potential ◽  
Sodium Pentobarbital ◽  
Sodium Barbital ◽  
Membrane Binding Sites ◽  
Drug Displacement ◽  
Compound Action

This study shows that Ca2+ reversed the nerve-blocking actions of procaine, lidocaine, procainamide, imipramine, chlorpromazine, tetrodotoxin, hexanol, heptanol, benzyl alcohol, thymol, sodium barbital, and sodium pentobarbital. Using the rat phrenic nerve, it was found that an elevation of external Ca2+ (from 0.22 mM to 4.4 mM) restored the blocked compound action potential of the nerve by around 30% for all three types of drugs: cationic, anionic, and uncharged.The high Ca2+ level of 4.4 mM displaced chlorpromazine from brain synaptosome membranes, but did not displace heptanol, pentobarbital, or lidocaine. Since there was no relation between blockade reversal and drug displacement by Ca2+, the data do not support the idea that Ca2+ and drugs compete for membrane-binding sites. Since approximately the same magnitude of reversal occurred with different drugs, as well as with tetrodotoxin, it is concluded that Ca2+ may cause a physiological kind of allosteric antagonism of the drug-blocked Na+ channel, or a direct augmentation of the Na+ conductance.

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