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PubMedDate not supplied

[Action of ketamine and hexenal on excitable membranes of a neuromuscular preparation in the frog].

The effects of the non-inhalation anesthetics, ketamine and hexenal (25 and 100 microM/l) on excitable membranes of the frog sartorius muscle were studied with the aid of intra- and extracellular electrodes. At the concentration 100 microM the anesthetics depressed most markedly the junctional transmission and practically had no influence on motor axon function. Since ketamine did not interact evidently with tubocurarine and showed pronounced antagonism to Mg ions, it is assumed that ketamine interferes with neuronally induced transmitter release.

Action Potentials↗

PubMed1984

Heavy metals: effects on synaptic transmission.

The acute effects of Pb++, Cd++ and Hg++ on synaptic transmission were studied on the in vitro sciatic nerve-sartorius muscle preparation of the frog, using electrophysiological techniques. Biochemical procedures were used to examine the effects of Pb++ and Cd++ on in vitro preparations of synaptosomes. In the electrophysiological studies Pb++ was shown to be a powerful competitive inhibitor of action potential-evoked release of acetylcholine (ACh) as judged by its depressant effects on the amplitude of endplate potentials (EPPs). The dissociation constant between Pb++ and the presynaptic Ca++ receptor is about 1 microM. Pb++ also increases spontaneous transmitter release as determined by the frequency of miniature endplate potentials (MEPPs). The increase in MEPP frequency is assumed to be due to an intracellular action of Pb++ to reduce the ability of nerve terminal organelles to buffer Ca++ and thereby, increases the intracellular concentration of Ca++. Cd++ also blocks evoked ACh release by a competitive inhibitory mechanism which appears similar to that for Pb++. The dissociation constant for Cd++ is about 2.8 microM. In contrast to Pb++, Cd++, does not increase resting MEPP frequency. Hg++ is unique in that it first causes an increase in evoked ACh release and then a sudden and complete blockade; the MEPP frequency follows a similar time course. The mechanism underlying these effects of Hg++ is uncertain. In rat brain synaptosomes, Pb++ and Cd++ competitively inhibit the K+-stimulated influx of 45Ca++. The dissociation constants for the interaction of Pb++ and Cd++ with Ca++ channels is 1.1 microM and 2.2 microM respectively. These data strongly support the idea that the electrophysiological effects of Pb++ and Cd++ on the EPP are due to a reduction of voltage-gated Ca++ entry into presynaptic nerve terminals.

Acetylcholine↗

PubMedDate not supplied

[Effect of chromium ions on the function of neuromuscular junctions].

It has been shown on neuro-muscular preparations of frog sartorius muscle that chromium ions in the concentrations 1-4 x 10(-6) g/ml strengthen spontaneous and evoked transmitter release. Cr3+ ions in the concentrations above 4 x 10(-6) g/ml decrease the membrane potential of muscle fibres, decrease the quantum content of the end plate potentials. Experiments on a single Ranvier node have shown that Cr3+ ions decrease the amplitude, increase the rate and duration of the action potential of a nerve fibre. It is concluded that chromium ions produce a pronounced effect on synaptic transmission, which differs significantly from the action of manganese, cobalt and nickel ions.

Action Potentials↗

PubMed1981

Dual action of meperidine on the frog neuromuscular junction: a prejunctional, opiate receptor-mediated depression of transmitter release and a postjunctional, nonopiate receptor effect on the endplate.

The action of meperidine was investigated on the frog sciatic nerve-sartorius muscle in vitro. Meperidine (5 X 10(-5) M to 2 X 10(-4) M) depressed the twitch response to nerve stimulation but potentiated the response to direct muscle stimulation. When the nerve terminal action potential and the endplate potential (EPP) were recorded simultaneously, the EPP was depressed by meperidine but only a small and variable decrease in the nerve terminal action potential was observed which did not produce the EPP depression. The depression of the EPP was partly antagonized by naloxone (3 X 10(-8) M). Meperidine also depressed the EPP produced by iontophoresis of acetylcholine onto the endplate, but this depression was not antagonized by naloxone. It is concluded that there are two meperidine actions on junctional transmission in this preparation. One, a depression of the prejunctional transmitter release process. This depression is partly, if not completely, opiate receptor-mediated. The second is a depression of the response of the endplate to acetylcholine. The latter effect does not involve a naloxone-sensitive opiate receptor.

Acetylcholine↗

PubMed1982

Structure-activity relationships of amantadine. I. Interaction of the N-alkyl analogues with the ionic channels of the nicotinic acetylcholine receptor and electrically excitable membrane.

In this study the effects of amantadine (1-adamantanamine) and its N-alkyl-substituted analogues [N-methyl- (NMA), N-ethyl- (NEA), N-propyl- (NPA), N-butyl- (NBA), and N,N-diethyl-amantidine (NNDEA)] were investigated on ionic channels of the electrically excitable membrane and of the nicotinic acetylcholine (ACh) receptors in frog sartorius muscles and on the binding of perhydrohistrionicotoxin (H12-HTX) to isolated membranes of the electric organ of the electric ray Torpedo. Amantadine and each analogue blocked the indirectly elicited twitch, but NPA, NBA, and NNDEA also potentiated the directly elicited twitch. The order of potency in inhibiting the indirect twitch was: NEA = NPA = NNDEA (10 microM) greater than NMA (15 microM) greater than NBA (40 microM) much greater than amantadine (130 microM). Neither amantadine nor its N-alkyl analogues affected miniature end-plate potential frequency or resting membrane potential but decreased miniature end-plate potential amplitude. Each compound prolonged the directly elicited action potential but did not alter delayed rectification. All of the compounds induced a concentration-dependent depression of the peak end-plate current (EPC) amplitude at negative membrane potentials and induced nonlinearity in the response at membrane potentials more negative than -40 mV. The order of potency in inhibiting the EPC (at -90 mV) was NNDEA (less than 0.5 microM) greater than NPA (less than 1.0 microM) greater than NBA (less than 2.0 microM) greater than NEA (19 microM) greater than NMA (42 microM) greater than amantadine (64 microM). Only NPA, NBA, and NNDEA depressed the peak EPC amplitude at positive membrane potentials as well. The shortening of the time constant of EPC decay by all compounds was concentration-dependent. At the higher concentrations examined, the slope of the relationship between the time constant of decay and membrane potential was reversed for all compounds. Only NPA induced a double-exponential decay of the EPC at positive membrane potentials. Neither amantadine nor its N-alkyl analogues inhibited the binding of [3H]ACh to its receptor in Torpedo electroplax but they inhibited the binding of [3H]H12-HTX binding to the ionic channel sites of the ACh receptor. The Ki for inhibition of [3H]H12-HTX binding was NEA = NNDEA (15 microM) greater than NMA (30 microM) greater than NPA = NBA (40 microM) greater than amantadine (60 microM). A gross correlation exists between their ability to block the indirect muscle twitch, miniature end-plate potential amplitude, peak EPC amplitude and the binding of [3H]H12-HTX. But, no correlation was found between these potencies and their antiviral activity. It is suggested that these compounds may interact with the ionic channel of the ACh receptor in its open and closed conformation.

Action Potentials↗

PubMed1983

[Multimodality in the amplitude distribution of miniature endplate potentials due to the action of spatially discrete areas of transmitter release].

Miniature end plate potentials (MEPPs) were simultaneously recorded in frog sartorius muscle by two intracellular microelectrodes. Some isolated groups of points (clouds) were found on the diagram of MEPPs scatter. Several peaks each of which was composed of signals from certain clouds (or from several clouds) on the scatter diagram were found on the histograms of MEPPs amplitude distribution. It is assumed that the clouds on the scatter histogram and the peaks on the histogram of MEPPs amplitudes are formed at the cost of secretion of quantum acetylcholine from spatial separate areas of transmitter release. The data obtained do not correspond with the subquantum hypothesis of transmitter release in neuromuscular junctions.

Animals↗

PubMed1983

[Analysis of polymodality in the distribution of latent periods and amplitudes of single-quantum synaptic potentials in the frog neuromuscular junction].

Intracellular recording with low concentrations of Ca2+ ions as analysed in the histograms of latency values and amplitude distributions, revealed 4-7 peaks in unitary potentials from the neuromuscular junction in the frog sartorius muscle. The increase of Ca2+ ions concentration led to disappearance of the multimodality. Extracellular recording revealed but a single mode in histograms of distributions. The number of modes in latency values distributions was found to have a positive correlation with values of the binominal parameter n and the number of peaks in histograms of the EP amplitudes. The peaks in histograms of distribution of the latency values and amplitudes of unitary EPs seem to reflect the action of transmitter release in the nerve terminals.

Action Potentials↗

PubMed1984

[Analysis of factors limiting the applications of binomial statistics in studies of mediator secretion at neuromuscular synapses].

Binomial parameters of transmitter secretion were calculated on the basis of synaptic potential analyses at frog sartorius muscle. In some synapses negative values of parameter of the p were found. These negative values often occurred at low concentrations of Ca2+ ions and small amplitude of miniature end plate potentials. The obtained data were interpreted in terms of a model which presupposes the heterogeneity of the quantum transmitter release at different sites. A computer imitation of transmitter secretion showed that the appearance of the negative p parameter values and erroneous n estimations in the experiment are related with the shape of the distribution of quantum transmitter release probability and the amplitude of miniature end plate potentials.

Animals↗

PubMed1984

Increase in transmitter release from motor nerve terminals induced by some pyridine derivatives.

The effects of 4-nitropyridine (4-NP), 4-aminopyridine-N-oxide (4-AP-N-O), 4-hydroxypyridine (4-HP), 2,6-diaminopyridine (2,6-DAP), 2,4-dihydroxypyridine (2,4-DHP) and pyridine on isolated sciatic nerve-sartorius muscle preparations were studied by means of intracellular and extracellular recording techniques. In junctions treated with (+) tubocurarine, 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP reversibly increased the amplitude and the latency of end-plate potentials (EPPs) and induced repetitive EPPs in response to single nerve impulses. As shown by extracellular focal recordings, the increase in latency of EPPs was due to a prolongation of the minimum synaptic delay, while the appearance of repetitive EPPs was the result of repetitive firing of motor nerve terminals. 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP increased dose-dependently the quantal content of EPPs, while 2,4-DHP and pyridine were found to be inactive. Comparison of the apparent rank order of potency in increasing quantal transmitter release indicates that the relative activity of the different pyridine derivatives studied is unrelated to their pK values. Spontaneous quantal transmitter release in resting junctions was unaffected by 4-NP, 4-AP-N-O, 4-HP and 2,6-DAP when applied at concentrations that enhanced evoked transmitter release. 4-NP differed from the other pyridine derivatives by producing in high concentrations a time-dependent increase in miniature end-plate potential frequency and a depolarization of the muscle fibres. In addition, 4-AP-N-O, 4-HP and 2,6-DAP were found to have no effect on MEPP frequency accelerated by increasing the external K+ concentration. In conclusion the data presented strongly suggest that 4-NP, 4-HP, 4-AP-N-O and 2,6-DAP facilitate evoked transmitter release from motor nerve terminals by a presynaptic action that seems related to an increased calcium influx secondary to the blockade of potassium channels in the nerve terminal.

Acetylcholine↗

PubMed1981

Tetrodotoxin, saxitoxin, chiriquitoxin: new perspectives on ionic channels.

Chiriquitoxin is a new, natural analog of tetrodotoxin, differing only in having the -CH2OH on C-6 replaced with an unidentified group of 104 mass units. On isolated frog sartorius muscle fibers, chiriquitoxin is equipotent with tetrodotoxin in blocking the Na+ channel, as shown by their identical dose-response relations on the maximum rate of rise of the action potential. Chiriquitoxin additionally interferes with some K+ channels, as shown by a slowed repolarization of the action potential, a reduced steady-state membrane conductance in current-clamped fibers, and a reduced K+ current in point-voltage-clamped fibers. The effects of chiriquitoxin on the Na+ and K+ channels are apparently exerted by the same molecule because high concentration of tetrodotoxin can either prevent or reverse the effects of chiriquitoxin on the K+ channel. Therefore, the receptor for tetrodotoxin-chiriquitoxin is probably not located inside the Na+ channel, but is on the outside surface of the membrane close to the orifice of the Na+ channel. The results also suggest that the Na+ and K+ channels are probably not randomly distributed throughout the membrane, but occur in clusters with some definite spatial relation to each other. From the structure of tetrodotoxin and a presumed structure of chiriquitoxin, the Na+ and K+ channels are estimated to be separated from each other by not less than 5 nor much more than 15A. The receptor for saxitoxin may be different, but partially overlapping with that for tetrodotoxin-chiriquitoxin.

Action Potentials↗

PubMed1982

Interactions of d-tubocurarine with the nicotinic acetylcholine receptor/channel molecule.

The interactions of d-tubocurarine (d-TC) with the ionic channel of the nicotinic acetylcholine receptor were studied by biochemical methods in Torpedo electric organ membranes and by electrophysiological methods on frog sciatic nerve-sartorius muscle preparation. Torpedo membranes were treated with alpha-bungarotoxin to inhibit the acetylcholine receptor sites, then binding of [3H]perhydrohistrionicotoxin to the ionic channel sites was studied and found to be inhibited by d-TC. At 37 degrees C, the Ki of d-TC was 10 microM, and at 22 degrees C it was 100 microM. The affinity of d-TC for the ionic channel sites relative to that of perhydrohistrionicotoxin was constant at temperatures from 2-20 degrees C, but increased at higher temperatures up to 37 degrees C. The peak endplate current amplitude was depressed with 1 to 2 microM d-TC in a voltage-dependent manner, with considerable departure from linearity at 10 and 30 degrees C. The effect of d-TC on spontaneous miniature endplate currents was similar and slightly more potent. The time constant of endplate current decay was decreased by d-TC (1 and 2 microM) at temperatures of 10, 15 and 30 degrees C. The channel lifetime was reduced by d-TC, but channel conductance was unaffected. It is suggested that d-TC interacts with both the acetylcholine receptor sites as well as its ionic channel sites in closed and open conformations.

Amphibian Venoms↗

PubMed1982

Mg++ antagonism of a prejunctional opiate receptor mediated effect at the frog neuromuscular junction.

The effect of meperidine on the spontaneous release of acetylcholine (mepp amplitude and frequency) and on the release evoked by nerve stimulation (epp amplitude and quantal content) was investigated in frog sciatic nerve-sartorius muscle in vitro. Meperidine (8.5 X 10(-5) or 1.6 X 10(-4)M) had no effect on mepp frequency recorded intracellularly in the absence of neuromuscular blockers, but reduced mepp amplitude. This depression was not antagonized by 3 X 10(-8) M naloxone and was explained by a nonspecific depressant action of meperidine on the endplate. When mepps and epps were recorded intracellularly in the presence of high Mg++, the mean amplitudes of both potentials were reduced equally by meperidine (either 1.6 or 4.2 X 10(-4)M) i.e. there was no change in the quantal content, and 3 X 10(-8)M naloxone failed to antagonize these amplitude depressions. When epps were recorded in the presence of d-tubocurarine, the percentage depression of epp amplitude by meperidine was significantly greater than found in the presence of Mg++ and was partially antagonized by naloxone indicating an opiate receptor mediated effect of meperidine. Thus it was concluded that Mg++ prevents this prejunctional opiate receptor mediated depressant effect of meperidine on the evoked release of acetylcholine.

Acetylcholine↗

PubMed1983

Calcium antagonism of an opiate drug effect on an excitable cell membrane.

When frog sartorius muscles are exposed to methadone (2-4 X 10(-4) M) the action potential recorded intracellularly is depressed and eliminated in 3 to 4 hr. This is due to a decrease in the sodium conductance as measured by the maximum rate of rise of the action potential. When the calcium concentration in frog Ringer's solution (normally 1.08 mM) was either lowered to 0.54 mM or raised to 2 mM, the effect of methadone on excitability was unchanged. However, increasing the extracellular calcium to 4 mM decreased the action of methadone. As this would also increase the intracellular calcium concentration, in other experiments the free intracellular Ca+ concentration was raised by adding 0.4 mM caffeine to the Ringer's solution. This also antagonized the depressant action of methadone. The antagonistic action of caffeine was not due to a direct effect of caffeine on sodium conductance because the administration of caffeine by itself caused a 10% depression of the action potential maximum rate of rise and caffeine did not antagonize the action of tetrodotoxin, which is a specific sodium channel blocking agent. Finally, it was shown that the calcium ionophore, A23187, in low concentrations antagonized the depressant actions of methadone and meperidine on action potential production. It was concluded that increasing the intracellular free calcium concentration antagonized the depressant effect on excitability produced by opiate drugs acting on an intracellularly oriented opiate drug receptor.

Action Potentials↗

PubMed1982

Meproadifen reaction with the ionic channel of the acetylcholine receptor: potentiation of agonist-induced desensitization at the frog neuromuscular junction.

The actions of the nicotinic noncompetitive antagonist meproadifen on both the acetylcholine (ACh) receptor-ion channel complex and electrically excitable membrane were examined in frog sciatic-nerve sartorius muscle preparations. Meproadifen (10-25 microM) blocked the nerve-evoked twitch without affecting the directly evoked twitch, the threshold, overshoot, amplitude, rate of rise, or falling phase of the directly elicited action potential in muscle. This suggests that this agent, at the concentrations that affect the nicotinic receptor, had negligible effect on the excitable membrane. In addition, the drug did not affect either the quantal content or quantal size of the end-plate potential. Meproadifen caused a voltage- and time-dependent decrease in the peak amplitude of the end-plate current (EPC) without significantly shortening the time constant of EPC decay. The voltage- and time-dependent effects of meproadifen were more pronounced at more negative potentials, as evidenced by hysteresis loops and nonlinearity in the current-voltage relationship of the EPC. Both hysteresis and nonlinearity in the current-voltage relationship of the EPC were eliminated when brief conditioning pulses were used for stepwise changes of membrane potentials. The decay time constant of the EPC in the presence of meproadifen remained an exponential function of time. Meproadifen blocked iontophoretically elicited EPCs but did not affect single-channel lifetime, conductance, or the decay time constant of the miniature EPC. Thus, the blockade was more marked on iontophoretically elicited EPCs than on miniature EPCs. Meproadifen also caused desensitization of both the junctional and extrajunctional ACh receptors, but, more important, meproadifen accelerated steady-state desensitization by several-fold (compared with the agonist). The marked depression of peak EPC amplitude and miniature EPC, its high affinity for the binding sites in the presence of the agonist, and acceleration of agonist-induced desensitization suggest that meproadifen interacts with the ACh-bound but nonconducting state of the ACh receptor-ion channel complex. Therefore, it appears that meproadifen interacts with the closed ionic channel of the ACh receptor in its resting and activated but nonconducting states, and only slightly affects the open conformation of the ionic channel.

Animals↗

PubMedDate not supplied

The pathogenesis of infectious bursal disease: serologic, histopathologic, and clinical chemical observations.

Infectious bursal disease in 35-day-old specific-pathogen-free (SPF) chickens was characterized clinically by its acute onset and brief duration. Clinical signs included depression, anorexia, diarrhea, and polyuria. A detectable precipitin antibody response occurred between 3 and 5 days postinoculation. Evaluation of pooled serum samples obtained from infectious bursal disease virus (IBDV)-infected chickens revealed transient changes in potassium, cholesterol, uric acid, lactate dehydrogenase, serum glutamic-oxalic transaminase, and serum proteins. Individual serum samples analyzed for uric acid concentration indicated that several IBDV-infected chickens had serum uric acid concentrations above the normal comparison range. Histopathologic examination of lymphoid and nonlymphoid tissues from IBDV-infected SPF chickens affirmed that the predominant lesion was lymphoid necrosis in the bursa of Fabricius. Other lymphoid organs were much less severely affected and possessed greater regenerative potential. Nonspecific and relatively mild changes were found in the liver and kidney: hepatic lipidosis and necrosis, renal intratubular crystalline deposits (probably urates), and increased ectopic lymphoid foci. There was no evidence of immune-complex-mediated arteritis/vasculitis in the sartorius muscle or any other tissue examined. Histopathologic and ultrastructural evidence of glomerulonephritis was rare but compatible with acute immune complexemia.

Animals↗

PubMed1984

Interaction of bicyclo-octane analogs of amantadine with ionic channels of the nicotinic acetylcholine receptor and electrically excitable membrane.

A series of bicyclo-octane analogs of amantadine was investigated for their actions on ionic channels of electrically excitable membrane and of nicotinic acetylcholine receptors in frog sartorius muscles. Amantadine and three of its amine-substituted bicyclo-octane analogs (ID 11, 33 and 36) blocked neuromuscular transmission in a concentration-dependent manner. The dipropylaminomethyl analog (ID 36) also potentiated the directly elicited twitch concurrent with a prolongation of the directly elicited action potential; there was no block of delayed rectification. The peak amplitude of the end-plate current at -90 mV was reduced in a nearly equipotent manner by amantadine and ID 11, 33 and 36, but these three analogs were more potent than amantadine in shortening the time constant of end-plate current decay. The pattern of nonlinearity in the current/voltage relationship and area of negative slope conductance coupled with the depression and shortening of the end-plate current suggest that these analogs block neuromuscular transmission by interacting with the ionic channel of the acetylcholine receptor. Because carboxy-substituted analogs were ineffective and amine-substituted ones were effective, it appears that the site(s) which controls the opening and closing of the ionic channel require(s) a drug to penetrate a lipid barrier to a hydrophilic site in the membrane.

Action Potentials↗

PubMed1984

Interaction of analogs of histrionicotoxin with the acetylcholine receptor ionic channel complex and membrane excitability.

The effects of the four N-benzylazaspiro analogs of histrionicotoxin, which are without the two side-chains typical of histrionicotoxin, were studied on the ionic channels of electrically excitable membrane and the nicotinic acetylcholine receptors in frog sartorius muscles. Each analog reversibly blocked the indirectly elicited twitch and potentiated the directly elicited twitch in a concentration-dependent manner. The analogs decreased the amplitude and rate of rise and prolonged the falling phase of the directly elicited action potential and blocked delayed rectification suggesting blockade of sodium and potassium conductances. All of the analogs caused a concentration- and voltage-dependent depression of the peak end-plate current amplitude and induced nonlinearity but no hysteresis or time dependency in the current-voltage relationship. The marked shortening of the time constant of end-plate current decay produced by the analogs was concentration-dependent. The relationship between the time constant of end-plate current decay and membrane potential remained a single exponential function of time despite the marked shortening of the decay phase and loss of voltage dependence. The effect of the analogs on miniature end-plate current was identical to that on end-plate current. Single channel conductance was unaffected by the analogs, but the single channel lifetime was shortened. The marked shortening of the time constant of the end-plate current decay and single channel lifetime plus linear relationship between reciprocal of the time constant of decay and analog concentrations strongly suggest that the analogs interact with the ionic channels of the nicotinic acetylcholine receptor in their open conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1984

The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties.

The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat. Pyr at concentrations of 0.2-0.4 mM potentiated the indirect evoked muscle twitch and at concentrations greater than or equal to 0.8 mM depressed the indirect twitch with an IC50 of about 2 mM. Twitch depression produced by Pyr was reversed slowly, and after a 60-min wash only 59% of the control muscle twitch had returned. Pyr did not affect either the membrane potential or the muscle action potential. Pyr had several effects at the neuromuscular junction of the frog and rat. It decreased the peak amplitude of the end-plate current (EPC) in a voltage- and concentration-dependent manner. In contrast to diisopropylfluorophosphate, which depresses the EPC amplitude and induces a double exponential decay of the EPC and miniature end-plate current (MEPC), Pyr produced a marked prolongation of the time constants of EPC and MEPC decay while maintaining a single exponential decay. The decrease caused by Pyr of indirect twitch tension, EPC amplitude, and ACh sensitivity indicates mechanisms which limit the number and/or properties of conducting channels. The drug decreased channel conductance and prolonged channel lifetime as revealed by Fourier analysis of ACh-induced end-plate current fluctuations. An altered form of the conducting species induced by Pyr appears to be responsible for either the apparent agonist-induced depolarization or its ability to increase the affinity of ACh for its recognition site. Pyr was also found to inhibit the binding of ACh and alpha-bungarotoxin to receptor-rich membrane from the electric organ of Torpedo nobiliana, and to have a higher affinity for the receptor than for the ion channel binding sites. These actions are distinct from acetylcholinesterase inhibition caused by the agent. Strong evidence suggests that the direct influences of the agent on neuromuscular transmission involve at least three distinct, although possibly interacting, mechanisms: (a) a weak agonist action, (b) the formation of desensitized receptor-complex intermediates, and (c) the alteration of the conductance properties of active channels.

Animals↗