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E G Rowan

Publications and source records attributed to E G Rowan.

At least 37 records · Page 2Linked to original sources
PubMed1997

This histamine-like effects of Phallusia nigra extract: evidences for direct activity at H1 receptors.

The methanol extract (mol. wt lower than 3,000 Da) of the sea squirt Phallusia nigra has stimulatory activity on guinea-pig ileum preparations. This effect was inhibited by cyproheptadine and mepyramine, but not be atropine. Mepyramine antagonized competitively the extract activity with a pA2 of 10.09 +/- 1.12, suggesting a direct activity on H1 histamine receptors. The extract was also assayed on guinea-pig right atria, however, only a mild increase in spontaneous contractions was observed compared to histamine, showing that the extract was a rather poor activator of cardiac H2 receptors. Histamine was not detected upon TLC analysis of the extract by comparison with an authentic standard.

Animals↗
PubMed1996

The prejunctional inhibitory effect of suramin on neuromuscular transmission in vitro.

The P2 purinoceptor antagonist suramin reverses skeletal muscle paralysis evoked by non-depolarizing neuromuscular blocking agents in vitro and in vivo. To further study the action of suramin on neuromuscular transmission, (miniature) endplate potentials ((m.)e.p.ps), motor nerve terminal currents and the release of radiolabeled acetylcholine was measured in isolated nerve-muscle preparations. In preparations paralysed by low Ca2+/high Mg2+ conditions, suramin (10 microM-1 mM) induced a concentration-dependent decrease in quantal content of the e.p.ps without affecting m.e.p.ps. Suramin reversed neuromuscular block by d-tubocurarine in these preparations. In erabutoxin paralysed preparations, suramin (40 microM-1 mM) inhibited the motor nerve terminal currents related to Ca2+ influx concentration-dependently, but did not affect Na+ currents. Suramin-induced inhibition of Ca2+ currents was not antagonized by ATP gamma S. Suramin (300 microM) reduced [14C]acetylcholine outflow in non-paralysed rat phrenic nerve-hemidiaphragm preparations by 32%. As suramin did not chelate Ca2+, these results indicate that suramin inhibits neuromuscular transmission by blocking prejunctional Ca2+ channels, thereby decreasing acetylcholine release upon nerve stimulation.

Acetylcholine↗
PubMed1996

Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia.

1. The electrophysiological actions of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), 2-methylthio ATP (2-meSATP) and alpha, beta-methyleneATP (alpha, beta-meATP) and of uridine 5'-triphosphate (UTP) were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-6 day old rat dorsal root ganglia. 2. ATP (10 nM-100 microM) applied rapidly via a U-tube perfusion system (equilibration time < 10 ms) activated concentration-dependent inward currents with a latency to onset of a few ms, an EC50 of 719 nM and a Hill slope of 1.47. 3. 2-meSATP (10 nM- 100 microM) and alpha, beta-meATP (100 nM - 100 microM) also evoked transient inward currents. The EC50 and Hill slopes were 450 nM and 1.58 for 2-meSATP and 1.95 microM and 1.53 for alpha, beta-meATP respectively. There was no significant difference between the maximum currents evoked by the three agonists. 4. As the concentration of ATP increased so the rate of rise and decay of the currents also increased. At 100 and 300 nM ATP the decay of the current was best fitted by a single exponential, but at 1 microM and above two exponentials were required. Log-log plots of the rise time or time constants of decay versus concentration were linear. Currents evoked by 2-meSATP and alpha, beta-meATP showed a similar concentration-dependence in their kinetics. 5. Inward currents evoked by ATP, 2-meSATP and alpha, beta-meATP (300 nM) were abolished by the P2-purinoceptor antagonist, suramin (100 microM). 6. UTP (10 microM) evoked similar transient inward currents, which were sensitive to suramin (100 microM). ATP (10 microM), applied 2 min beforehand, reduced the response to UTP (10 microM) by 80 +/- 10%. 7. This study shows that ATP, 2-meSATP and alpha, beta-meATP act via a suramin-sensitive P2x-purinoceptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The pyrimidine nucleotide, UTP, was also active. It is likely that the agonists were acting at the P2x3-subtype to produce these effects.

Adenosine Triphosphate↗
PubMed1996

Toxins affecting K+ channels.

Potassium channels are involved in modulating the excitability of neurones by regulating the membrane potential, or by affecting the amount of neurotransmitter released from nerve terminals. Potassium channels are highly diverse and can be activated by either voltage or increased intracellular calcium concentration. The potassium channel forms a highly selective membrane pore. Four subunits each with six membrane-spanning regions (S1-S6) are required to produce a functional pore. Molecular biologists have cloned more than 50 different potassium channel subtypes. Naturally occurring protein toxins have been used to pharmacologically characterize native and cloned potassium channels.

Calcium Channels↗
PubMed1995

Modification of ionic currents underlying action potentials in mouse nerve terminals by the thiol-oxidizing agent diamide.

The effect of diamide, a thiol-oxidizing agent, was tested using electrophysiological techniques to determine whether its ability to alter neuromuscular transmission in vitro could be attributed to alterations of ion channels controlling neuronal excitability and/or acetylcholine release. In mouse triangularis sterni preparations, diamide transiently increased the evoked release of acetylcholine and then blocked release. Extracellular recording of perineural waveforms associated with neuronal action potentials at motor nerve terminals showed that diamide reduced the waveforms associated with the delayed rectifier K+ current, a Ca2+ current and a Ca(2+)-activated K+ current (IK,Ca). Inhibition of quantal transmitter release was not associated with failure of action potentials to invade nerve terminals. Thus, diamide modifies the ionic currents underlying the nerve terminal action potential, some of these changes probably account for the complex effects of diamide on quantal transmission.

Acetylcholine↗
PubMed1995

Structure-activity studies on scorpion toxins that block potassium channels.

Scorpion venoms contain toxins that block different types of potassium channels. Some of these toxins have affinity for high conductance Ca(2+)-activated K+ channels and for dendrotoxin-sensitive voltage-dependent K+ channels. The structural features that determine the specificity of binding to different channel types are not known. We investigated this using natural and synthetic scorpion toxins. We have tested the effects of charybdotoxin (CTX) and two homologues (Lqh 15-1 and Lqh 18-2), iberiotoxin (IbTX), and kaliotoxin (KTX) from the scorpions Leiurus quinquestriatus hebreus, Buthus tamulus and Androctonus mauretanicus mauretanicus, respectively, and synthetic variants of CTX, namely CTX2-37, CTX3-37, CTX4-37, and CTX7-37, on a Ca(2+)-activated K+ current (IK-Ca) at a mammalian motor nerve terminal, and on the binding of a radiolabelled dendrotoxin, 125I-DpI, to voltage-dependent K+ channels on rat brain synaptosomal membranes. The native toxins contain 37-38 amino acid residues, they are over 30% identical in sequence (CTX and IbTX are 68% identical), and they have similar three-dimensional conformations. All toxins, except IbTX, displaced 125I-DpI from its synaptosomal binding sites: Lqh 18-2 (Ki = 0.25 nM), KTX (Ki = 2.1 nM), CTX (Ki = 3.8 nM), CTX2-37, (Ki = 30 nM), Lqg 15-1 (Ki = 50 nM), CTX3-37 (Ki = 60 nM), CTX4-37 (Ki = 50 nM), CTX7-37 (Ki = 105 nM). IbTX had no effect at 3 microM. When variants of CTX with deletions at the N-terminal portion were tested for their activity on IK-Ca on motor nerve terminals in mouse triangularis sterni nerve-muscle preparations, CTX3-37 and CTX4-37 were ineffective at 100 nM; and CTX7-37 was ineffective at up to 1 microM. IbTX and CTX (100 nM) completely blocked IK-Ca, but KTX (100 nM) did not affect the nerve terminal IK-Ca. Different residues appear to be important for interactions of the toxins with different K+ channels. IbTX did not displace dendrotoxin binding, but it did block IK-Ca, whereas KTX was as active as CTX against dendrotoxin binding but it did not affect the IK-Ca of the motor nerve terminals. The N-terminal section of the toxins appears to be particularly involved in block of IK-Ca at the motor nerve terminal: it is truncated in the inactive synthetic CTX variants; and it is positively charged at lysine-6 in KTX (which is inactive), but negatively charged in IbTX and neutral in CTX.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1995

Ammodytoxin A acceptor in bovine brain synaptic membranes.

Ammodytoxin A, the presynaptic neurotoxin from Vipera ammodytes ammodytes venom, was found to bind specifically and with high affinity to bovine cortex synaptic membrane preparation. The detected ammodytoxin A high-affinity binding was characterized by equilibrium binding analysis which revealed a single high-affinity binding site with Kd 4.13 nM and Bmax 6.67 pmoles/mg of membrane protein. 125I-ammodytoxin A was covalently cross-linked to its neuronal acceptor using a chemical cross-linking technique. As revealed by subsequent SDS-PAGE analysis and autoradiography, 125I-ammodytoxin A specifically attached to membrane components with apparent mol. wts 53,000-56,000. Besides by the native ammodytoxin A, the binding of radioiodinated ammodytoxin A to the neuronal acceptor was highly attenuated, also by other two iso-neurotoxins from V. a. ammodytes venom, ammodytoxins B and C, and neurotoxin crotoxin B from the venom of the South American rattlesnake (Crotalus durissus terrificus). Vipera berus berus phospholipase A2 was a weaker inhibitor, whereas nontoxic phospholipase A2, ammodytoxin I2 and myotoxic phospholipase A2 homologue, ammodytin L, both from V. a. ammodytes venom as well, were very weak inhibitors. No inhibitory effect on 125I-ammodytoxin A specific binding at all was, however, obtained with alpha-dendrotoxin, beta-bungarotoxin and crotoxin A, respectively. Treatment of synaptic membranes with proteinase K and Staphylococcus aureus V-8 proteinase, a combination of PNGase F and neuroaminidase, heat or acid lowered the 125I-ammodytoxin A specific binding to various extents but never completely abolished it. The ammodytoxin A binding site in bovine synaptic membranes is thus most likely a combination of membrane glycoprotein acceptor and membrane phospholipids. As ammodytoxin A reduced the second negative component of the perineural waveform, measured on mouse triangularis sterni preparation, which is very likely a result of an inhibition of a fraction of the terminal K+ currents, the ammodytoxin A acceptor could well be connected with K+ channels.

Animals↗
PubMed1995

Some pharmacological studies on the effects of Cerastes vipera (Sahara sand viper) snake venom.

The effects of the venom of the Sahara sand viper (Cerastes vipera) were studied on isolated chick biventer cervicis, isolated rat atria and vas deferens preparations, and on the electrocardiogram of anaesthetized rats. Effects on 3H-noradrenaline uptake were studied using rat brain synaptosomes. At 50 micrograms/ml and 100 micrograms/ml, the venom caused a transient increase in rate and force of contractions of the rat atria followed by an irreversible depression. These effects were not prevented by atenolol, atropine or a combination of the two. In the presence of 25 microM lignocaine, the effects of venom on rat atria were reversible by washing. At 100 micrograms/ml, the venom transiently increased responses of vas deferens preparations to indirect stimulation, but had little effect on responses to noradrenaline, KCl, and ATP. In the presence of an alpha 1-adrenoceptor antagonist (prazosin) or a P2-purinergic receptor antagonist (suramin), the venom still significantly increased twitch height and responses to noradrenaline but not to KCl or ATP. The effect of the venom did not change after exposure to a combination of prazosin, suramin and tetrodotoxin. The venom (100 micrograms/ml) significantly decreased twitches to indirect and direct stimulation in chick biventer cervicis preparations. Responses to exogenously applied acetylcholine, carbachol and KCl were also decreased. Venom blocked the synaptosomal uptake of 3H-noradrenaline (IC50 = 5 micrograms/ml), and caused severe bradycardia in vivo. Some of the direct effects on muscle preparations are possibly due to the venom's phospholipase A2 activity.

Adrenergic alpha-Antagonists↗
PubMed1995

The effects of two phospholipase A2 inhibitors on the neuromuscular blocking activities of homologous phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake.

Previous studies have shown that homologous phospholipases A2 (PLA2) (Pa-3, Pa-9C, Pa-10F and Pa-11) from the venom of the Australian king brown snake, Pseudechis australis, significantly reduce the resting membrane potentials and quantal contents of endplate potentials recorded from endplate regions of mouse triangularis sterni nerve-muscle preparations. It is not clear whether PLA2 activity is essential for their neuromuscular activities. Therefore, pharmacological studies were carried out to determine whether neuromuscular activity of the toxins changed after treatment with the phospholipase A2 inhibitors 7,7-dimethyl-eicosadienoic acid (DEDA) and manoalide. After incubation of the toxins with manoalide (120 nM), or DEDA (50 microM), no PLA2 activity against 1-stearoyl 2-[3H]arachidonoylglycerophosphocholine was detected. After incubation with manoalide and/or DEDA, the toxins did not depolarize muscle fibre membranes up to 60 min after administration. However, manoalide and DEDA had different influences on the inhibitory effect of these toxic enzymes on acetylcholine release from nerve terminals. Manoalide abolished the inhibitory effect of the toxins on evoked release of acetylcholine. In contrast, DEDA was not able to prevent the reduction of quantal content of endplate potentials induced by the toxins. This study provides evidence that the depolarizing action and the inhibitory effect on release of acetylcholine exerted by these toxic PLA2 from king brown snake are independent phenomena. The evidence for this conclusion was that inhibition of enzymatic activity with an arachidonic acid analogue (DEDA) abolished the depolarizing effect of the toxins but not the effects on the quantal release of acetylcholine from mouse motor nerve terminals. The data suggest that the depolarizing effect of these toxins is probably due to the enzymatic activity. Since manoalide interacts with lysine residues of PLA2 polypeptides, and, as shown here, manoalide prevented inhibition of neurotransmitter release, lysine residues may play an important role in the inhibitory activity of these toxins.

Acetylcholine↗
PubMed1994

On the site by which alpha-dendrotoxin binds to voltage-dependent potassium channels: site-directed mutagenesis reveals that the lysine triplet 28-30 is not essential for binding.

We constructed a synthetic gene encoding the published amino acid sequence of DTx from Dendroaspis angusticeps, a ligand of voltage-dependent postassium channels that facilitates neurotransmitter release. We expressed it in Escherichia coli as a fusion protein secreted in the culture medium. The recombinant DTx was generated in vitro by chemical treatment and recovered as two isoforms. One of them (rDTx), like the venom toxin, has an N-terminal pyroglutamate whereas the other (rQDTx) has a free N-terminal glutamine. Chromatographic differences between rDTx and natural DTx led us to re-examine the amino acid sequence of natural DTx. In contrast to what was previously published, position 12 was an Asp and not Asn. Despite this difference, rDTx and DTx had similar toxicity in mice and binding affinity to synaptosomes, suggesting that residue 12 is not important for DTx function. Nor is the N-terminal residue implicated in DTx function since rDTx and rQDTx also had similar biological activities. We also synthesized and expressed a mutant of the DTx gene in which the lysine triplet 28-30 was changed into Ala-Ala-Gly. The two resulting recombinant isoforms exhibited only small decreases in biological activity, excluding the possibility that the positively charged lysine triplet 28-30 of DTx is directly involved in the toxin functional site.

Amino Acid Sequence↗
PubMed1994

The effects of five phospholipases A2 from the venom of king brown snake, Pseudechis australis, on nerve and muscle.

The effects on vertebrate neuromuscular function of five homologous phospholipases A2 (PLA2) (Pa-3, Pa-8, Pa-9C, Pa-10F and Pa-12B) from the venom of the Australian king brown snake, Pseudechis australis, were determined. These isoenzymes (0.2-1.6 microM) reduced, with different potencies, responses of chick biventer cervicis preparations to nerve stimulation and to exogenously applied acetylcholine, carbachol and KCl in a time- and concentration-dependent way but with different potencies. They also blocked twitches of mouse hemidiaphragm preparations evoked by nerve and by direct muscle stimulation. Pa-8 was the most active and Pa-9C was the least potent. There was a strong correlation between the enzymatic activity and the effect of toxins on the responses of mouse hemidiaphragm to direct muscle stimulation, but weak correlation between the effects on indirect responses and enzymatic activity. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations showed that Pa-10F and Pa-12B at 0.2 microM significantly reduced quantal content after 10 min. Pa-8 (0.2 microM) reduced the amplitude of endplate potentials by about 25% and abolished miniature endplate potentials within 15 min. Pa-3 (0.2 microM) and Pa-9C (0.8 microM) also significantly reduced quantal content by about 30% of control after 30 min. Among these toxins, Pa-3 and Pa-8 at 0.2 microM depolarised mouse muscle fibres after 30 min. Extracellular recording of action potentials at motor nerve terminals of mouse triangularis sterni preparations indicated that these isoenzymes reduced the waveforms associated with both Na+ and K+ conductances. Since no facilitatory effect on the release process has been observed, the apparent blockade of K+ conductance by some of these toxins may not be a selective action on K+ channels, but may be secondary to membrane depolarisation. An in vivo study with Pa-8 and Pa-10F demonstrated myotoxic effects. Light microscopic examination showed a degeneration of mouse and rat skeletal muscle fibres caused by Pa-8 and Pa-10F. For the in vivo study, rats received 80 micrograms/kg of the toxins s.c. and mice were injected i.m. with the toxins (40 micrograms/kg). Myotoxicity appears to be the predominant effect of these five toxins.

Acetylcholine↗
PubMed1994

The pharmacological effects of cadmium on skeletal neuromuscular transmission.

1. Cadmium (100 microM) blocks neuromuscular transmission by blocking prejunctional voltage dependent calcium channels in a competitive manner. 2. Prolonged exposure to cadmium leads to a block of neuromuscular transmission that is not competitive. 3. Cadmium can increase the spontaneous release of acetylcholine, this release is modified by the cation composition of the bathing solution. 4. Cadmium may enter the nerve terminal via the voltage dependent calcium channels (the L-type calcium channel has been implicated) and exert some of its actions intracellularly. 5. All of the extracellular effects of cadmium can be reversed by cysteine.

Acetylcholine↗
PubMed1994

Interactions between suxamethonium and non-depolarizing neuromuscular blocking drugs.

In anaesthetized cats, we have confirmed that previously injected suxamethonium potentiates non-depolarizing neuromuscular blocking drugs whereas, when injected during the block, suxamethonium antagonizes the paralysis. We have attempted to explain these interactions by studying the effects of suxamethonium on extracellularly recorded nerve ending waveforms that correspond to the ionic currents in the mouse triangularis sterni isolated nerve-muscle preparation. The preparations were paralysed with mu-conotoxin (obtained from the cone snail), which is believed to act by selectively blocking sodium channels in muscle, and which therefore should not interfere with currents at the nerve endings. Suxamethonium, in concentrations of 0.5-300 mumol litre-1, produced a concentration-dependent increase in the amplitude of the waveform corresponding to the inward calcium current evoked by a nerve impulse. This effect did not occur in the presence of tubocurarine, suggesting that suxamethonium, which is a nicotinic agonist, may have been acting on a nicotinic receptor on the nerve endings that is coupled to the voltage-operated calcium channels. The inward calcium current is believed to be responsible for neurotransmitter (acetylcholine) release. It is concluded, therefore, that its enhancement by suxamethonium contributes to the ability of this drug to reverse non-depolarizing block. Suxamethonium also exerted complex effects on the waveform corresponding to the outward flowing calcium-activating potassium current at the nerve endings, but no effect was observed in this isolated nerve-muscle preparation that could obviously explain the ability of suxamethonium to potentiate subsequently injected non-depolarizing blocking drugs.

4-Aminopyridine↗
PubMed1993

Effects of scorpion (Buthus tamulus) venom on neuromuscular transmission in vitro.

The effects of venom from the Indian red scorpion Buthus tamulus (BT) on neuromuscular transmission have been investigated by means of twitch tension and electrophysical recording techniques using isolated skeletal muscle preparations. On chick biventer cervicis preparations, BT (1-3 micrograms/ml) augmented the twitch responses to indirect, but not direct, muscle stimulation. Higher concentrations caused a transient augmentation followed by a large contracture and then a reduction in twitch height. BT at the concentrations tested caused little change in postjunctional sensitivity as assessed by responses to exogenous acetylcholine, carbachol and KCl. Tubocurarine abolished the prolonged contracture induced by BT (10 micrograms/ml) in the presence or absence of nerve stimulation. On mouse hemidiaphragm preparations, BT (3-10 micrograms/ml) increased the twitch responses to indirect stimulation but caused little change in directly stimulated preparations. On mouse triangularis sterni preparations, BT (3-10 micrograms/ml) increased quantal content of the evoked end-plate potentials (epps) by about 70%, without markedly affecting the time course and amplitude of miniature epps. BT also caused repetitive epps in response to single shock nerve stimulation. Extracellular recording of nerve terminal current waveforms in triangularis sterni preparations revealed that BT (10-30 micrograms/ml) slightly reduced the amplitude of the waveform. Subsequently, BT induced repetitive firing of nerve endings in response to single shock stimulation, and eventually markedly prolonged the time course of the nerve terminal waveform. The effects caused by BT were different from those caused by iberiotoxin, the blocker of Ca(2+)-activated K+ currents, isolated from BT. The effects were similar to those caused by ATX-II, a toxin that delays inactivation of Na+ channels. However, BT and ATX-II behaved differently in the presence of K+ channel blockers, 3,4-diaminopyridine (DAP) and tetraethylammonium (TEA). These results confirm that Buthus tamulus venom acts mainly prejunctionally to increase the release of acetylcholine. The effect of BT on the perineural waveforms suggests that some of its actions may be due to effects on Na+ channels at or near the nerve terminals; however, additional effects of K+ channels are likely.

Animals↗
PubMed1993

Prejunctional action of neostigmine on mouse neuromuscular preparations.

We have studied the effects of neostigmine on the mouse diaphragm and triangularis sterni isolated nerve-muscle preparations. Mechanical responses of the muscle, end-plate potentials and miniature end-plate potentials, and extracellularly recorded nerve ending currents were recorded. In the mouse diaphragm nerve-muscle preparations, neostigmine 1 mumol litre-1 continued to produce some antagonism of tubocurarine-induced block after cholinesterase had been inactivated completely by diisopropyl fluorophosphate 22 mumol litre-1. In the mouse triangularis sterni preparation, neostigmine 0.1-1 mumol litre-1 increased the quantal content of the end-plate potential in a concentration-dependent manner. This effect appeared to be sufficient to account for the cholinesterase-independent antagonistic action to tubocurarine under the conditions of the experiments. Neostigmine 1-100 mumol litre-1 depressed the amplitude of the K+ currents of the perineural waveforms in a concentration-dependent manner, and this may account for its ability to increase the quantal content of the end-plate potential. Although inhibition of acetyl-cholinesterase is the main mechanism of action of neostigmine, the drug also exerts an additional direct action on motor nerve endings to block the delayed rectifier K+ channels and enhance transmitter release. This effect occurred at clinically relevant concentrations of neostigmine. Physostigmine and pyridostigmine did not possess this additional action.

Animals↗
PubMed1992

Neuromuscular effects of four phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake.

Four homologous single chain phospholipases A2 (Pa-1G, Pa-5, Pa-12C and Pa-15) were tested for neuromuscular effects on chick biventer cervicis and mouse hemidiaphragm nerve-muscle preparations. The four isozymes blocked directly elicited (mouse hemidiaphragm) and indirectly elicited (mouse and chick nerve-muscle preparations) twitch responses in concentrations of 1-30 micrograms/ml. The order of potency seen in both types of preparations was Pa-1G = Pa-5 greater than Pa-12C much greater than Pa-15. All four isozymes caused slow-onset, sustained contractures and reduction of muscle membrane potentials. In the chick preparation, responses to acetylcholine, carbachol and KCl were reduced by exposure to the toxins. It is concluded that the toxins act primarily postsynaptically to depress muscle contractility, perhaps by directly damaging muscle fibres. The order of potency agrees with their phospholipase A2 activity. Pa-1G is unusual because it is an acidic molecule, most toxic phospholipases being basic.

Animals↗
PubMed1992

The effects of Indian red scorpion Buthus tamulus venom in vivo and in vitro.

The Indian red scorpion Buthus tamulus (or Mesobuthus tamulus) can cause fatal envenoming, but its mechanism of action is unclear. Venom was tested in vivo in anaesthetized rats and in vitro on isolated cardiac and skeletal muscle preparations. In vivo, the venom caused marked rhythmical fluctuations in blood pressure preceding cardiovascular collapse and death. On sheep Purkinje fibres, venom could induce spontaneous action potentials and cause prolongation of action potential duration. In chick biventer cervicis and mouse triangularis sterni preparations, venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials in response to single shock stimulation. High concentrations caused stimulation then block of neuromuscular transmission. The main effects of Buthus tamulus venom are likely to be due to toxins that affect the opening of Na+ channels in nerves and muscles. This will cause an increase in the release of neurotransmitters in the peripheral nervous system, which may produce cardiovascular abnormalities and respiratory paralysis.

Action Potentials↗