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

(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.

2019 ◽  
Vol 24 (4) ◽  
pp. 668-673
Author(s):  
Serkan Cizmeciogullari ◽  
Yasar Keskin ◽  
N. Hale Saybasili ◽  
Selcuk Paker

2004 ◽  
Vol 114 (1) ◽  
pp. 1-16 ◽  
Author(s):  
NIZAMETTIN DALKILIC ◽  
HULAGU BARISKANER ◽  
NECDET DOGAN ◽  
ILHAMI DEMIREL ◽  
BARKIN ILHAN

1988 ◽  
Vol 60 (6) ◽  
pp. 2168-2179 ◽  
Author(s):  
D. L. Eng ◽  
T. R. Gordon ◽  
J. D. Kocsis ◽  
S. G. Waxman

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.


1978 ◽  
Vol 56 (6) ◽  
pp. 1063-1066 ◽  
Author(s):  
Peter L. Carlen ◽  
Allan L. Staiman ◽  
William A. Corrigall

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.


Sign in / Sign up

Export Citation Format

Share Document