Goniopora Toxin Research Articles

Effects of goniopora toxin on the action potential and membrane currents of guinea-pig single ventricular cells

The effects of Goniopora toxin (GPT), a polypeptide isolated from a coral, Goniopora spp., on action potential and membrane currents were studied in single ventricular cells of the guinea-pig using the whole-cell clamp technique with a single patch electrode. GPT at a concentration of 10 nmol/l prolonged the duration of the action potential without significant change in the resting membrane potential and action potential amplitudes. This prolongation became more evident at lower stimulus frequencies and persisted after washing with toxin-free solution. Tetrodotoxin (TTX, 1 mumol/l), but not Co2+ (2 mmol/l), abolished the prolonged action potential. Under voltage-clamp conditions, a sustained inward current, not present in the control, followed the transient inward current during depolarizing pulses in the GPT-treated cells. The current-voltage relationship for the sustained inward current was much the same as that for the fast sodium current reported in rat single ventricular cells (Brown et al. 1981). Both the sustained and transient currents were abolished by the shift of holding potential in the direction of depolarization and reappeared after repolarization; the reappearance of the sustained current was much slower than that of the transient current. TTX but not Co2+ abolished both the sustained and transient inward currents. Calcium current and time-independent current were not affected by GPT. Time-dependent outward current induced by large depolarizing pulses was attenuated by GPT.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of effects of carbachol on the Na-Ca exchange mechanism in frog atrial muscle treated with goniopora toxin.

Carbachol (CCh) at a concentration of 10(-7) M completely inhibited the twitch contraction of frog atrial muscle. However, when the preparation was treated with goniopora toxin (GPT), a selective inhibitor of Na channel inactivation, and the twitch contraction was augmented through the activation of Na-Ca exchange by this toxin, the reduction in contractile amplitude by CCh was only about 30% even at higher concentrations. The maximum rate of rise of the twitch contraction was not affected by CCh in GPT-treated preparations. The time course of configuration change of the twitch contraction after application of CCh in GPT-treated muscle indicated that the attenuation of amplitude preceded the shortening of duration. The residual contraction under the combined treatments with GPT and CCh was abolished by removal of external Ca++ or addition of TTX. CCh only moderately shortened the action potential which was prolonged by GPT, and further addition of TTX abolished the action potential. From these results, we suggest that CCh does not influence the twitch contraction which is augmented via the activation of the Na-Ca exchange mechanism in frog atrial muscle.

Lack of Effects of Carbachol on the Na-Ca Exchange Mechanism in Frog Atrial Muscle Treated with Goniopora Toxin

Lack of Effects of Carbachol on the Na-Ca Exchange Mechanism in Frog Atrial Muscle Treated with Goniopora Toxin

P-33 - Amino acid sequence of Goniopora toxin

P-33 - Amino acid sequence of Goniopora toxin

A polypeptide toxin from the coral Goniopora: Purification and action on Ca 2+ channels

A polypeptide toxin has been isolated from Goniopora coral with an M r of 19000. Goniopora toxin has the following properties: (i) it induces contraction of guinea pig ileum and this contraction is prevented by Ca 2+-channel blockers; (ii) it stimulates 45Ca 2+ influx in cardiac cells in culture and this stimulation is abolished by Ca 2+-channel blockers; (iii) it prevents binding of (+)-[ 3H]PN 200-110 to the Ca 2+-channel protein of skeletal muscle T-tubule membranes. All these results taken together suggest that Goniopora toxin is a Ca 2+-channel activator.

P-94 - Effects of goniopora toxin on the action potential and membrane currents of guinea-pig single ventricular cells

The effects of Goniopora toxin (GPT), a polypeptide isolated from a coral, Goniopora spp., on action potential and membrane currents were studied in single ventricular cells of the guinea-pig using the whole-cell clamp technique with a single patch electrode. GPT at a concentration of 10 nmol/l prolonged the duration of the action potential without significant change in the resting membrane potential and action potential amplitudes. This prolongation became more evident at lower stimulus frequencies and persisted after washing with toxin-free solution. Tetrodotoxin (TTX, 1 μmol/l), but not Co2+ (2 mmol/1), abolished the prolonged action potential. Under voltage-clamp conditions, a sustained inward current, not present in the control, followed the transient inward current during depolarizing pulses in the GPT-treated cells. The current-voltage relationship for the sustained inward current was much the same as that for the fast sodium current reported in rat single ventricular cells (Brown et al. 1981). Both the sustained and transient currents were abolished by the shift of holding potential in the direction of depolarization and reappeared after repolarization; the reappearance of the sustained current was much slower than that of the transient current. TTX but not Co2+ abolished both the sustained and transient inward currents. Calcium current and time-independent current were not affected by GPT. Time-dependent outward current induced by large depolarizing pulses was attenuated by GPT. From these results, it is suggested that GPT predominantly acts on the sodium channels in cardiac muscle, to give rise to a sustained sodium current which is responsible for the prolongation of action potential, and that the sodium channels modified by this toxin may reveal slow inactivation and slow recovery from inactivation as compared with those of unmodified sodium channels.

Effects of goniopora toxin on bullfrog atrial muscle are frequency-dependent

When goniopora toxin (GPT), a marine toxin isolated from coral, was applied to the bullfrog atrial muscle, the duration of action potential (APD) was prolonged, and a positive inotropic effect was produced. Such effects of GPT were influenced by stimulus frequency. At lower frequencies of 0.1 Hz, GPT (10 to 100 nmol/l) produced a moderate prolongation of APD and positive inotropic effect. At higher frequencies (1.0 Hz), however, the effects of GPT on both APD and contraction were suppressed. In contrast, APD and duration of contraction were prolonged with long intervals of stimulation (1-3 min), in the presence of GPT. The rested-state contraction was also markedly increased and prolonged by GPT. When the membrane potential was conditioned by voltage clamp pulses, the prolonged action potential in GPT-treated muscle was shortened in proportion to the increase in conditioning depolarization. However, the shortening effect of conditioning depolarization was attenuated by lengthening the resting period after the conditioning depolarization. These results, in conjunction with our previous results, suggest that the frequency-dependent effects of GPT on APD and contraction reflect time- and and membrane potential-dependent changes of the toxin-modified sodium channels.

Effects of Goniopora toxin on the membrane currents of bullfrog atrial muscle.

The effects of Goniopora toxin (GPT), isolated from the Goniopora species, on the action potential and membrane currents of bullfrog atrial muscle were studied using the double sucrose-gap method. GPT at concentrations above 10 nmol/l prolonged the duration of the action potential and sometimes induced arrhythmias. The prolongation was also induced in the presence of Ca channel blockers (Mn or verapamil). These effects were not reversed by continuous superfusion of GPT-free solution, but were rapidly antagonized by tetrodotoxin (1 mumol/l). The resting potential was not affected by GPT. Voltage clamp experiments revealed that sustained inward current flows following the fast sodium current upon depolarization, in the presence of GPT. The current was elicited by the toxin in Mn-treated fibers and abolished in the presence of TTX. The delayed outward current (Ix) was slightly reduced; the background K current (IK1), inward background current (Ib) and slow inward current (Islow) were not altered by GPT. These results suggest that GPT acts on sodium channels to give rise to a prolonged sodium current which is in turn responsible for the prolongation of the action potential.

S1-3) - Goniopora toxin and other natural products affecting ionic channels

S1-3) - Goniopora toxin and other natural products affecting ionic channels

P-300) - Frequency-dependent action of goniopora toxin on action potential of bullfrog atrial muscle

P-300) - Frequency-dependent action of goniopora toxin on action potential of bullfrog atrial muscle

Frequency-dependent action of goniopora toxin on electromechanical properties of bullfrog atrial muscle

Frequency-dependent action of goniopora toxin on electromechanical properties of bullfrog atrial muscle

Effects of goniopora toxin on the gating mechanisms of sodium channel in crayfish giant axon.

Goniopora toxin (GPT) prolonged the action potential duration of crayfish giant axon. Since the prolongation was selectively suppressed by tetrodotoxin and procaine, it was suggested that GPT acts on the sodium channel and prolongs the action potential duration. In the present study, we examined the effects of GPT on the gating mechanisms of sodium channel in crayfish giant axons by using a double sucrose gap-voltage clamp method. GPT (100 nM), when applied externally, markedly slowed the falling phase of transient sodium current during a step depolarization. The falling phase consisted of two components which showed different time constants (0.5 - 2 msec and 10 -20 msec) after treatment with GPT. The tail current observed upon repolarization was also slowed. However, the kinetics of activation and steady-state inactivation of sodium current were little affected. These results indicate that GPT acts on the inactivation- and deactivation-processes of sodium channel and produces a sustained sodium current. In contrast, internal application of GPT produced no effect on the sodium channel, suggesting that GPT is effective only from the outside of axon.

Effects of goniopora toxin on the action potential and membrane currents of bullfrog atrial muscles.

Effects of goniopora toxin (GPT), a marine polypeptide isolated from a coral, Goniopora spp., on the action potential and membrane currents of the bullfrog atrial muscles were studied using the double sucrose-gap method. Under current clamp conditions, GPT (100 nM) prolonged the duration of action potential and sometimes induced arrhythmias. These effects were not reversed by continuous perfusion of GPT-free solution or by Ca-antagonists (MnCl2, verapamil), but restored by TTX(1 μM). Results obtained with voltage clamp expeiments are as follows: GPT slowed the inactivation of fast sodium current(INaf) and slightly decreased the delayed outward current (IX). However, the slow inward current(ISi), background K current(IKl), and inward background current(Ib) were not changed by GPT. From these results, it was concluded that GPT prolonged the action potential by inhibiting the inactivation of fast channel and inducing the sustained sodium influx. In addition, a slight decrease of the delayed outward current(IX) seems to contribute to the prolongation of action potential.

Effects of goniopora toxin on non‐adrenergic, non‐cholinergic response and purine nucleotide release in guinea‐pig taenia coli

1. Effects of goniopora toxin (GPT) on non-adrenergic, non-cholinergic inhibitory responses were examined in isolated guinea-pig taenia coli and the transmission mechanism was analysed.2. GPT (20-50 nM) gradually augmented the relaxation and rebound contraction induced by electrical transmural stimulation in the presence of guanethidine and atropine. These effects were abolished by tetrodotoxin.3. The resting tension and the response to exogenously applied ATP were little affected by GPT.4. The action potentials and the electrotonic potentials recorded by a double sucrose-gap method were little affected by GPT.5. These results indicate that the augmentation is elicited by a direct action of GPT on the non-adrenergic, non-cholinergic neurones, rather than on the smooth muscles per se.6. GPT augmented the amplitude of the inhibitory junction potential (i.j.p.) recorded in the presence of guanethidine and atropine. GPT also enhanced the (3)H efflux in response to electrical transmural stimulation of preparations pre-loaded with [(3)H] adenosine. Tetrodotoxin markedly inhibited or abolished the i.j.p. and (3)H efflux.7. These results would suggest that augmentation of the non-adrenergic, non-cholinergic responses is due to increased transmitter release from the nerve. Under conditions in which the transmitter release was augmented, the non-adrenergic, non-cholinergic response showed an essentially similar pattern to that obtained under normal conditions; therefore the inhibitory response is probably due to a putative transmitter, possibly ATP or a related nucleotide.

O-26 - Effects of goniopora toxin on nicotine-induced responses in the adrenergic nerve terminals

O-26 - Effects of goniopora toxin on nicotine-induced responses in the adrenergic nerve terminals

Relationship between the effects of Goniopora toxin on action potential and on contractile force in guinea-pig papillary muscle.

Effects of Goniopora toxin (GPT) on cardiac action potential and on contractile force were investigated in isolated guinea-pig papillary muscle. GPT produced a positive inotropic effect by increasing contractile force and prolonging the relaxation time. The time-to-peak force was little affected. GPT prolonged the action potential duration but did not affect the resting membrane potential nor the amplitude of the action potential. Thus there was a correlation between the positive inotropic effect and prolongation of the action potential duration. Tetrodotoxin or a reduction in extracellular sodium concentration attenuated both the positive inotropic effect and the prolonged duration of the action potential induced by GPT. Lanthanum or a reduction in extracellular calcium concentration also inhibited the increased contraction but did not shorten the prolonged durations of contraction and action potential. Verapamil attenuated the positive inotropic effect by reducing both the contractile force and the duration of contraction, but did not shorten the action potential duration. These results show that the positive inotropic effect of GPT depends on the increase in both sodium and calcium influxes while the prolonging effect on the action potential probably depends only on an increase in sodium influx. Hence, it is concluded that the prolongation of the action potential due to the increased sodium permeability is an essential process for the appearance of the positive inotropic effect of GPT.

RELATIONSHIP BETWEEN THE EFFECTS OF GONIOPORA TOXIN ON ACTION POTENTIAL AND ON CONTRACTILE FORCE IN GUINEA-PIG PAPILLARY MUSCLE

AbstractEffects of Goniopora toxin (GPT) on cardiac action potential and on contractile force were investigated in isolated guinea-pig papillary muscle. GPT produced a positive inotropic effect by increasing contractile force and prolonging the relaxation time. The time-to-peak force was little affected. GPT prolonged the action potential duration but did not affect the resting membrane potential nor the amplitude of the action potential. Thus there was a correlation between the positive inotropic effect and prolongation of the action potential duration. Tetrodotoxin or a reduction in extracellular sodium concentration attenuated both the positive inotropic effect and the prolonged duration of the action potential induced by GPT. Lanthanum or a reduction in extracellular calcium concentration also inhibited the increased contraction but did not shorten the prolonged durations of contraction and action potential. Verapamil attenuated the positive inotropic effect by reducing both the contractile force and the duration of contraction, but did not shorten the action potential duration. These results show that the positive inotropic effect of GPT depends on the increase in both sodium and calcium influxes while the prolonging effect on the action potential probably depends only on an increase in sodium influx. Hence, it is concluded that the prolongation of the action potential due to the increased sodium permeability is an essential process for the appearance of the positive inotropic effect of GPT.

P-59) - Effect of goniopora toxin on crayfish giant axon

P-59) - Effect of goniopora toxin on crayfish giant axon

Effects of Goniopora toxin on guinea-pig blood vessels.

Effects of a marine polypeptide, Goniopora toxin (GPT) (molecular weight 12,000), were examined in isolated blood vessels guinea pigs. GPT, ranging from 10-100 nM, augmented the contractile response to electrical transmural stimulation in the thoracic aorta, portal vein, and mesenteric and femoral arteries. The effects were abolished by tetrodotoxin and bretylium, and were markedly attenuated by phentolamine. As GTP did not affect the resting tension spontaneous rhythmicity or noradrenaline-induced contraction, the toxin appears to act on the neural elements in the vascular wall rather than on the smooth muscle. In the portal vein preloaded with 3H-noradrenaline, GPT enhanced the 3H-efflux in response to electrical transmural stimulation, yet had not effect on the spontaneous efflux. The increase in stimulation-evoked 3H-efflux caused by GPT was more than 15 times larger than the increase seen with cocaine or phentolamine. Tetrodotoxin completely blocked the 3H-efflux induced by electrical transmural stimulation. These data suggest that GPT acts on nerve components in guinea pig blood vessels and increases the release of noradrenaline evoked by electrical stimulation of the nerve fibers. These effects are probably associated with prolongation of the action potential duration and repetitive discharges in the adrenergic nerve fibers.

P-9 - Relationship between the effect of Goniopora toxin on action potential and contractile force in guinea pig papillary muscle

P-9 - Relationship between the effect of Goniopora toxin on action potential and contractile force in guinea pig papillary muscle