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.

Different Sites of Membrane Action for Tetrodotoxin and Lipid-Soluble Anesthetics

1975 ◽  
Vol 53 (4) ◽  
pp. 513-524 ◽  
Author(s):  
A. L. Staiman ◽  
P. Seeman
Keyword(s):  
Benzyl Alcohol ◽  
Binding Sites ◽  
Compound Action Potential ◽  
Additive Effects ◽  
Tertiary Amines ◽  
Nerve Membrane ◽  
Membrane Action ◽  
Frog Sciatic Nerve ◽  
Membrane Binding Sites ◽  
Compound Action

1. To examine whether different local anesthetics act on different or similar sites in the nerve membrane, the effects of combinations of lipid-soluble anesthetics and tetrodotoxin (TTX) were studied on the compound action potential of the frog sciatic nerve.2. The nerve-blocking potency of TTX was potentiated 5-fold by benzyl alcohol and 10-fold by lidocaine, at concentrations of these latter two drugs which were just barely anesthetic; no such synergism occurred between saxitoxin (STX) and TTX, their combined effect being merely additive.3. Simple additive effects also occurred between benzyl alcohol and phenol, benzyl alcohol and urethane, as well as lidocaine with a spirosuccinimide, RAC 109 II.4. Synergism occurred between STX and 2-aminobenzimidazole.5. A small but consistent synergism occurred between lidocaine and benzyl alcohol.6. It is concluded that uncharged anesthetics, tertiary amines, and TTX act via different membrane binding sites which are all closely associated with the Na+ conductance channels.

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.

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.

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