[Blockage of autonomous ganglia with tetraethylammonium salts; pharmacology & effects of tetraethylammonium].
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Autonomic Nervous System↗
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[Study of tetraethylammonium bromide in obstetrics and gynecology: tetraethylammonium in labor].
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Ammonia↗
Tetraethylammonium ions block 5-HT3 receptor-mediated ion current at the agonist recognition site and prevent desensitization in cultured mouse neuroblastoma cells.
Effects of tetraethylammonium ions on 5-hydroxytryptamine3 (5-HT3) receptor-mediated ion current have been studied in whole-cell voltage clamped N1E-115 cells. Inward currents evoked by superfusion with 10 microM 5-HT are rapidly blocked by external tetraethylammonium and the kinetics of the partially blocked inward currents are slowed down. External tetraethylammonium also prevents, but is unable to reverse, agonist-induced desensitization of the 5-HT3 receptor-mediated ion current. Both effects depend on tetraethylammonium concentration and attain half maximum values at 2.6-2.8 mM tetraethylammonium. Tetraethylammonium acts externally, since substituting internal monovalent cations by 107 mM tetraethylammonium fails to block 5-HT3 receptor-mediated ion current. This ion substitution causes a shift in the current reversal potential towards a more positive value, indicating that the receptor-operated ion channel is permeable to tetraethylammonium. An IC50 effect of external tetraethylammonium is reduced to 28% blockade when currents are evoked by 50 microM instead of 10 microM 5-HT, indicating that tetraethylammonium and 5-HT compete for the same site. It is concluded that tetraethylammonium shows low affinity for (part of) the agonist binding site involved in the activation as well as in the desensitization of the receptor-operated ion channel.
Animals↗
Interleukin-1beta inhibits a tetraethylammonium-induced synaptic potentiation in the rat dentate gyrus in vitro.
The effect of the pro-inflammatory cytokine, interleukin-1beta on an NMDA receptor-independent form of synaptic plasticity brought about by the application of the K+ channel blocker tetraethylammonium, was examined in the rat dentate gyrus in vitro. Field excitatory postsynaptic potentials (EPSPs) were recorded from the medial perforant path of the dentate gyrus every 20 s. Perfusion of the K+ channel blocker, tetraethylammonium chloride (25 mM) for 10 min and subsequent washout gave rise to robust and long-term potentiation of the field EPSP slope (tetraethylammonium induced long-term potentiation; 125+/-5% of baseline 60 min following tetraethlylammonium-washout; n = 7, P < 0.05) Application of interleukin-1beta (1 ng/ml) for 30 min was found to inhibit the induction, but not the maintenance of the tetraethylammonium induced long-term potentiation (n = 8). Heat denatured interleukin-1beta had no effect on tetraethylammonium induced long-term potentiation (n = 6). The expression of tetraethylammonium induced long-term potentiation was found to be accompanied by an increase in the magnitude of paired pulse depression seen at interstimulus intervals of 20 and 100 ms (controls, 42+/-5% and 13+/-2%; tetraethylammonium, 62+/-5% and 22+/-2% respectively for both intervals; n = 6, P < 0.05). The increase in paired pulse depression at an interstimulus interval of 100 ms was significantly attenuated by pre-treatment of slices with interleukin-1beta. The inhibitory effect of interleukin-1beta on both tetraethylammonium induced long-term potentiation and the tetraethylammonium induced increase in paired pulse depression was antagonised by pre-incubation with the interleukin-1 receptor antagonist. Interleukin-1 receptor antagonist was found to have no effect on tetraethylammonium induced long-term potentiation when applied on its own (n = 5). The p38 mitogen activated protein kinase inhibitor SB203580 (4-(4-fluorophenyl)-2-(4 methylesulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was also found to inhibit the induction of tetraethylammonium induced long-term potentiation (n = 6). These findings suggest a possible role for interleukin-1beta in the modulation of NMDA receptor-independent synaptic plasticity in the rat dentate gyrus.
Animals↗
Nasal absorption of tetraethylammonium in rats.
The in vivo and in situ nasal absorption of tetraethylammonium in rats was studied. Following nasal administration of tetraethylammonium (150 mumol/kg) to rats, there was a rapid increase in plasma concentration of tetraethylammonium followed by a slow increase. The absolute bioavailability of nasal tetraethylammonium administration was 79%. In rats, tetraethylammonium was shown to be more efficiently absorbed from nasal mucosa than from intestine. In in situ nasal perfusion experiments, the nasal absorption rate of tetraethylammonium was reduced by an increase in perfusion volume. The plot of absorption rate constant against 1/volume did not result in a straight line. In addition, there was a concentration-dependent decline in the absorption rate of tetraethylammonium with an increase in its initial concentration in the perfusion solution. Choline and 2,4-dinitrophenol significantly inhibited the nasal absorption of tetraethylammonium. These data may suggest the existence of a carrier-mediated transport process of tetraethylammonium in nasal mucosa of rats.
2,4-Dinitrophenol↗
Carrier-mediated transport systems of tetraethylammonium in rat renal brush-border and basolateral membrane vesicles.
Transport of [3H]tetraethylammonium, an organic cation, has been studied in brush-border and basolateral membrane vesicles isolated from rat kidney cortex. Some characteristics of carrier-mediated transport for tetraethylammonium were demonstrated in brush-border and basolateral membrane vesicles; the uptake was saturable, was stimulated by the countertransport effect, and showed discontinuity in an Arrhenius plot. In brush-border membrane vesicles, the presence of an H+ gradient ( [H+]i greater than [H+]o) induced a marked stimulation of tetraethylammonium uptake against its concentration gradient (overshoot phenomenon), and this concentrative uptake was completely inhibited by HgCl2. In contrast, the uptake of tetraethylammonium by basolateral membrane vesicles was unaffected by an H+ gradient. Tetraethylammonium uptake by basolateral membrane vesicles was significantly stimulated by a valinomycin-induced inside-negative membrane potential, while no effect of membrane potential was observed in brush-border membrane vesicles. These results suggest that tetraethylammonium transport across brush-border membranes is driven by an H+ gradient via an electroneutral H+-tetraethylammonium antiport system, and that tetraethylammonium is transported across basolateral membranes via a carrier-mediated system and this process is stimulated by an inside-negative membrane potential.
Animals↗
Biphasic effect of tetraethylammonium on canine purkinje fibre action potential configuration.
1. Using conventional microelectrode techniques a biphasic effect of tetraethylammonium (5 mmol/l) on the configuration of action potentials recorded from isolated canine Purkinje fibres: action potentials were first shortened (early effect) and then lengthened (late effect) by tetraethylammonium. 2. The early effect of tetraethylammonium also included lengthening of phase 1 duration and elevation of the plateau amplitude. These early effects reached steady-state within the first 3 min of superfusion and were readily reversed within 3 min of initiating washout of the drug. 3. The late effect (gradual lengthening of repolarisation during phase 3) failed to reach steady-state within the initial 60 min of superfusion and was not reversible. 4. The early effects of tetraethylammonium were more marked at slow driving rates and were not affected by blockade of alpha- and beta-adrenoceptors using 1 mumol/l phentolamine and 1 mumol/l propranolol. 5. The early effects of tetraethylammonium were mimicked by 4-aminopyridine (0.5 mmol/l), and in the presence of 4-aminopyridine tetraethylammonium failed to induce further changes in action potential morphology. 6. The early effects of tetraethylammonium may be due to inhibition of the transient outward current. 7. The rapid onset and reversibility of these early effects suggest that tetraethylammonium may act from outside the cell membrane.
Action Potentials↗
Lamotrigine inhibits tetraethylammonium-induced synaptic plasticity in the rat amygdala.
Although long-term potentiation was generally initiated by a brief tetanus, in the hippocampus, it could also be evoked by application of the K+ channel blocker tetraethylammonium. The present study was aimed at investigating the effect of lamotrigine, a new anticonvulsant, on the tetraethylammonium-induced potentiation in brain slices of the rat amygdala using intracellular recording techniques. Bath application of tetraethylammonium (20 mM) for 10 min resulted in a long-lasting enhancement of the amplitude of excitatory postsynaptic potentials to 235 +/- 12% of control (n = 6, P < 0.001). Pretreatment of the slices with nifedipine (10 microM) abolished the potentiation, suggesting that tetraethylammonium long-term potentiation in the amygdala is due to Ca2+ influx through voltage-dependent Ca2+ channels. By contrast, N-methyl-D-aspartate receptor activation was not required because D-2-amino-5-phosphonovalerate (50 microM) did not prevent the tetraehylammonium long-term potentiation. Superfusion of lamotrigine (50 microM) depressed the excitatory postsynaptic potential to 53.8 +/- 3.9% of control. Tetraethylammonium was subsequently added in the presence of lamotrigine but failed to enhance the excitatory postsynaptic potential. Bursts of Ca2+ spikes evoked by a depolarizing pulse or by synaptic stimulation under tetraethylammonium were depressed by lamotrigine. It is concluded that lamotrigine is capable of inhibiting tetraethylammonium-induced synaptic plasticity. The underlying mechanism is likely due to lamotrigine's inhibition of postsynaptic voltage-dependent Ca2+ channels. Considering that tetraethylammonium is a convulsant agent and brief seizure episodes induced long-term potentiation, fibre sprouting and the development of aberrant synaptic contacts, lamotrigine could be a potential neuroprotective agent, especially in pathological situations where excessive glutamate release occurs.
Amygdala↗
Contractures elicited by tetraethylammonium in avian muscle treated with methohexitone.
1 The chick biventer cervicis muscle immersed in methohexitone (8.8 x 10(-5) M) responded to tetraethylammonium with contractures which were dose-related. The ED50 for tetraethylammonium was 2.1 x 10(-3) M. 2 In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations: these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres. 3 The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation. 4 Tubocurarine (1.2 x 10(-6) M) displaced the dose-response curve for tetraethylammonium-methohexitone-induced contractures to the right. The dose-ratio was 15.63 +/- 1.98. 5 Physostigmine (1.8 x 10(-6) M) potentiated the activity of tetraethylammonium-methohexitone 3.26 or 3.84 fold, depending on the method of calculation used. 6 Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium-methohexitone. 7 It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor.
Animals↗
Benefits of supplementing St Thomas' Hospital cardioplegic solution with tetraethylammonium on functional and metabolic recovery of isolated rat hearts.
This study was designed to evaluate whether the addition of potassium channel blockers, tetraethylammonium, 4-aminopyridine or glibenclamide, to St Thomas' cardioplegia improved myocardial preservation over that achieved by St Thomas' cardioplegic solution alone. Initially, isolated rat hearts were subjected to 30 min of continuous normothermic hypoxic cardioplegia. Control hearts were arrested with St Thomas' cardioplegia followed by tetraethylammonium, glibenclamide or 4-aminopyridine-enriched cardioplegia. Subsequently, in a second experiment, hearts were subjected to 45 min of normothermic global ischaemia, after 3 min of cardioplegia with either tetraethylammonium-enriched or standard St Thomas' cardioplegia. In both regimens, hearts arrested with tetraethylammonium-enriched St Thomas' cardioplegia showed better recovery of contractile function than controls (P<0.001). Creatine kinase levels were significantly lower in the tetraethylammonium group (P<0.001). 4-Aminopyridine treatment caused similar contractility to that of the control group but raised creatine kinase and lactate dehydrogenase levels (P<0.001). Glibenclamide diminished coronary flow autoregulation, and increased lactate dehydrogenase leakage in reperfusion (P<0.05) with similar contractility to controls. The results of this preliminary in vitro study demonstrate that, in rat heart, St Thomas' cardioplegia enriched with tetraethylammonium improves post-ischaemic contractile function and reduces creatine kinase release. It is concluded that high potassium blocks the membrane at the rapid depolarization phase with rapid sodium influx and tetraethylammonium further prevents repolarization by blocking voltage-dependent potassium channels.
4-Aminopyridine↗
Effects of tetraethylammonium, 4-aminopyridine and bretylium on cardiovascular tissues from normo- and hypertensive rats.
Our objective was to test whether potassium-channel blockade is a potential positive inotropic mechanism for heart failure. Thus we studied the effects of tetraethylammonium, 4-aminopyridine and bretylium on left ventricular action potentials, left ventricular contractility in the absence and presence of hypertrophy, and on isolated blood vessels from Wistar Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs). Tetraethylammonium at 10(-3)-10(-2) M, 4-aminopyridine at 10(-4)-10(-3) M and bretylium at 10(-6)-10(-4) M prolonged the action potentials of the WKY left ventricular strip. Similar concentrations of tetraethylammonium, 4-aminopyridine and bretylium augmented the peak force, prolonged the contractions, and did not cause arrhythmias in the absence or presence of isoprenaline on left ventricular strips from 12-month-old WKY. The 12-month-old SHR has hypertrophy of the left ventricle with reduced contractility and prolongation of relaxation. The effects of tetraethylammonium and bretylium were similar on WKY and SHR, whereas the effects of 4-aminopyridine were reduced on SHR left ventricular contractility, which suggests that the function of the transient outward-blocking potassium channel may be impaired in hypertrophy. Bretylium at < or = 10(-4) M had no effect on the portal vein, intralobar or mesenteric arteries. Tetraethylammonium and 4-aminopyridine at > or = 10(-5) M increased the duration or amplitude, or both, of the portal vein contractions. Tetraethylammonium at > or = 10(-2) M and 4-aminopyridine at > or = 3 x 10(-4) M contracted the mesenteric artery, and 4-aminopyridine also contracted the intralobar pulmonary artery. In summary, we have demonstrated that the action potential prolonging effects of potassium-channel blockade is associated with a positive inotropic effect on the rat left ventricle. The non-specific blockers, tetraethylammonium and 4-aminopyridine, do not have potential as positive inotropes in heart failure because of their widespread effects, including vasoconstriction. The potential of bretylium and some of the newer selective potassium-channel blockers as positive inotropes requires further evaluation.
4-Aminopyridine↗
Ganglionic blockade with tetraethylammonium in conscious rats.
The sympathetic ganglionic blocking agent tetraethylammonium has been used as a clearance marker for the measurement of renal plasma flow, but the sympathetic ganglionic blocking dose in rats is unknown. In light of differential reflex activation of sympathetic nerve activity to heart and kidney, we compared the effect of tetraethylammonium on renal nerve activity, mean arterial pressure, and heart rate. Conscious rats were infused with either vehicle (isotonic saline) or tetraethylammonium (n = 7 in both groups). Tetraethylammonium was infused cumulatively (35 minutes per dose) in the following doses: 10(-5), 10(-4), 10(-3), 10(-2), and 10(-1) g/kg body wt per hour. Doses for 15% reduction were 10(-1) for mean arterial pressure, 0.55 x 10(-1) for heart rate, and 0.055 x 10(-1) g/kg body wt per hour for renal nerve activity. Renal nerve activity was abolished at 10(-1) g/kg body wt per hour; mean arterial pressure and heart rate were unchanged at doses lower than 10(-1) g/kg body wt per hour. The lethal dose was 1 g/kg body wt per hour. No changes were observed in vehicle-treated animals. Tetraethylammonium at 10(-1) g/kg body wt per hour resulted in an attenuated increase in renal nerve activity during acetylcholine-induced reduction in mean arterial pressure, reflecting arterial baroreceptor inhibition. We conclude that renal nerve activity is 10- and 18-fold more sensitive to sympathetic ganglionic blockade than heart rate and mean arterial pressure, respectively. When tetraethylammonium is used as a clearance marker for measurement of renal plasma flow in rats, it should be administered in doses less than 10(-2) g/kg body wt per hour.
Animals↗
9-Aminoacridine- and tetraethylammonium-induced reduction of the potassium permeability in pancreatic B-cells. Effects on insulin release and electrical properties.
The effects of 9-aminoacridine and tetraethylammonium on insulin release and rubidium efflux from perifused rat islets were investigated and correlated with their effects on the electrical properties of mouse B cells studied with microelectrode techniques. 9-Aminoacridine (0.05--1 mmol/l) and tetraethylammonium (2--40 mmol/l) produced a dose-dependent, reversible potentiation of glucose-stimulated insulin release. This effect was rapid, affected both phases of secretion and was maximum in the presence of 6 mmol/l glucose, but no longer significant at 20 mmol/l glucose. It was unaltered by atropine or propanolol, and abolished by mannoheptulose or omission of extracellular calcium. 9-Aminoacridine, but not tetraethylammonium, also induced insulin release in the absence of glucose stimulation. Neither drug modified glucose metabolism in islet cells and only 9-aminoacridine increased 45Ca2+ uptake. In the presence of 0, 3 or 6 mmol/l glucose, but no longer at 20 mmol/l glucose, 9-aminoacridine and tetraethylammonium reduced the rate of 86Rb+ efflux from the islets. Both drugs also slightly reduced 86Rb+ uptake by islet cells. In the presence of 11 mmol/l glucose, 9-aminoacridine reduced the amplitude and the duration of the polarization phases between the bursts of electrical activity; concomitantly these periods of spike activity were markedly prolonged. At lower glucose concentrations (3 or 7 mmol/l), 9-aminoacridine progressively depolarized B cells and induced electrical activity in otherwise silent cells. Tetraethylammonium also suppressed the repolarization phases between the bursts of spikes in the presence of a stimulating concentration of glucose. At low glucose, tetraethylammonium produced only a limited and not maintained depolarization. These results show that a reduction of the potassium permeability in pancreatic B cells potentiates the insulin-releasing effect of glucose and may even stimulate secretion. They also suggest that the initial depolarizing effect of glucose is due to a reduction of the potassium permeability, whereas the repolarization at the end of each burst of electrical activity is mediated, at least in part, by an increase in the potassium permeability of B cells.
Aminacrine↗
Contrasting effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice.
Many different K+ channels have been identified in the gastrointestinal tract, and the two classical K+ channel blockers, tetraethylammonium and 4-aminopyridine, show different sensitivity for these channels. The aim of the present study was to compare the effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice. 4-Aminopyridine (5 mg/kg, p.o.) inhibited, but tetraethylammonium (40 mg/kg, p.o.) enhanced, the intestinal propulsion of a charcoal suspension in conscious mice. Studies in vitro showed that perfusion of 5 mM 4-aminopyridine increased the maximal contractile force and minimal relaxation force, and decreased the amplitude and frequency of the peristaltic contraction of the isolated duodenum. However, perfusion of 5 mM tetraethylammonium increased the maximal contractile force, the minimal relaxation force and the amplitude of the contraction. The effects of tetraethylammonium and 4-aminopyridine on the duodenal contraction could be abolished completely by application of 5 microM verapamil. Our results in vivo and in vitro showed that tetraethylammonium and 4-aminopyridine had contrasting effects on the gastrointestinal function of mice.
4-Aminopyridine↗
Fictive locomotor patterns generated by tetraethylammonium application to the neonatal rat spinal cord in vitro.
Intrinsic spinal networks generate a locomotor rhythm characterized by alternating electrical discharges from flexor and extensor motor pools. Because this process is preserved in the rat isolated spinal cord, this preparation in vitro may be a useful model to explore methods to reactivate locomotor networks damaged by spinal injury. The present electrophysiological investigation examined whether the broad spectrum potassium channel blocker tetraethylammonium could generate locomotor-like patterns. Low (50-500 microM) concentrations of tetraethylammonium induced irregular, synchronous discharges incompatible with locomotion. Higher concentrations (1-10 mM) evoked alternating discharges between flexor and extensor motor pools, plus large depolarization of motoneurons with spike broadening. The alternating discharges were superimposed on slow, shallow waves of synchronous depolarization. Rhythmic alternating patterns were suppressed by blockers of glutamate, GABA(A) and glycine receptors, disclosing a background of depolarizing bursts inhibited by antagonism of group I metabotropic glutamate receptors. Furthermore, tetraethylammonium also evoked irregular discharges on dorsal roots. Rhythmic alternating patterns elicited by tetraethylammonium on ventral roots were relatively stereotypic, had limited synergy with fictive locomotion induced by dorsal root stimuli, and were not accelerated by 4-aminopyridine. Horizontal section of the spinal cord preserved irregular ventral root discharges and dorsal root discharges, demonstrating that the action of tetraethylammonium on spinal networks was fundamentally different from that of 4-aminopyridine. These results show that a potassium channel blocker such as tetraethylammonium could activate fictive locomotion in the rat isolated spinal cord, although the pattern quality lacked certain features like frequency modulation and strong synergy with other inputs to locomotor networks.
4-Aminopyridine↗
Effect of sulfhydryl reagents on tetraethylammonium transport in rat renal brush border membranes.
Effect of sulfhydryl reagents on the transport of tetraethylammonium, an organic cation, has been studied in brush border membrane vesicles isolated from rat renal cortex. H+ gradient-dependent uptake of tetraethylammonium by the vesicles was inhibited by various sulfhydryl reagents in a dose-dependent manner, and the potency of the reagents was followed in the order of HgCl2 greater than p-chloromercuribenzoate, p-chloromercuribenzene sulfonate (PCMBS) greater than N-ethylmaleimide. In the absence of H+ gradient, tetraethylammonium uptake and efflux also were inhibited by p-chloromercuribenzoate and PCMBS. The sulfhydryl reagents did not affect the dissipation rate of H+ gradient across the membranes. Pretreatment of brush border membranes with PCMBS resulted in an inhibition of tetraethylammonium uptake in the presence and absence of H+ gradient, and this inhibition was reversed by subsequent treatment of the vesicles with thiols such as dithiothreitol, glutathione and cysteine. The inhibitory effect by PCMBS pretreatment was protected in the preincubation with unlabeled tetraethylammonium. These results suggest that sulfhydryl reagents inhibit the transport of tetraethylammonium by their specific interaction with the active sites of the carrier, and that sulfhydryl groups are essential for organic cation transport system in renal brush border membranes.
4-Chloromercuribenzenesulfonate↗
Moment analysis of drug disposition in kidney. III: Transport of p-aminohippurate and tetraethylammonium in the perfused kidney isolated from uranyl nitrate-induced acute renal failure rats.
A different manner of insufficiency of renal epithelial cell transport between the organic anion and cation, p-aminohippurate and tetraethylammonium, respectively, was observed in the perfused kidney isolated from uranyl nitrate-induced acute renal failure (ARF) rats. The single-pass outflow pattern of the perfused kidney was analyzed by noncompartmental moment analysis. The active tubular secretion was impaired faster than the reduction of glomerular filtration, and the tetraethylammonium secretion decreased at an earlier stage of ARF than p-aminohippurate. The apparent uptake rate constant from blood to cells of p-aminohippurate was reduced with the progress of ARF and associated with the amount of this drug secreted, whereas the uptake rate constant of tetraethylammonium did not change until the late stage of ARF. The mean residence time in renal epithelial cells of tetraethylammonium was prolonged with reduction of the amount to be secreted, while that of p-aminohippurate remained unchanged. Therefore, the uptake of p-aminohippurate across the basolateral membranes decreased gradually, and the transport across the brush border membranes was still unchanged after uranyl nitrate treatment. On the other hand, the secretion of tetraethylammonium from cells to lumen was impaired at first, and then the uptake from blood to cells was impaired. These results suggest that impairment by uranyl nitrate-induced ARF appears at the carrier-mediated transport process of the epithelial cell membranes for both organic anions and cations.
Acute Kidney Injury↗
The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle.
The actions of 3,4-diaminopyridine, 4-aminopyridine and tetraethylammonium were studied on the chick biventer cervicis muscle preparation. All three compounds produced a greater augmentation of indirectly elicited twitches than of directly elicited twitches. The compounds did not restore transmission in OmMCa2+ solutions but rather produced contractures that were inhibited by acetylcholine receptor antagonists. The compounds restored twitch height in one-tenth normal Ca2+ solutions and induced spontaneous muscle twitching. The compounds reversed dantrolene-induced block of directly elicited twitches. Interactions between tetraethylammonium and 3,4-diaminopyridine were also studied. In indirectly stimulated preparations, the combined effects of the two compounds were more than additive at one concentration level only. In directly stimulated preparations, the effects of 3,4-diaminopyridine were greatly enhanced by tetraethylammonium pretreatment. 3,4-Diaminopyridine pretreatment produced less synergism than tetraethylammonium pretreatment. It is concluded that the actions of the aminopyridines and tetraethylammonium on transmitter release and muscle contractility are essentially similar. These actions are postulated to arise from an inhibitory action on potassium conductance and on an ability to release calcium from nerve and muscle membranes. On the basis of the interaction studies, it is suggested that the compounds possess different binding capacities for two different sites on the potassium conducting channel.
Animals↗