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

Abstract

Abstract-Effectsof 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 con tractile 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.

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

“…These results are much the same as those observed in the preparations treated with GPT alone (10). Thus, it is likely that the twitch con traction observed after treatments with GPT and CCh is also produced mainly through a Na-Ca exchange mechanism, as suggested in GPT-treated preparations (9,10).…”

“…Previously, we reported that GPT prolonged the action potential of frog atrial muscle by inhibiting the inactivation process of the Na channel and induced the positive inotropic effect due to the secondary activation of the Na-Ca exchange mechanism (9,10). In the present study, also, GPT prolonged the action potential and twitch contraction, and it increased the contractile amplitude.…”

“…Previously, we reported that goniopora toxin (GPT), a polypeptide isolated from coral, prolonged the action potential and produced a positive inotropic effect in mammalian and frog cardiac muscles (8)(9)(10)(11). The underlying mechanisms are the inhibition of Na channel inactivation (10,12), causing the increase in Na influx and the subsequent activation of the Na-Ca exchange mechanism.…”

Mechanism of action of nicotine in isolated urinary bladder of guinea‐pig

“…However, in some tissues, TTX has been reported not to inhibit the response to nicotine. These findings suggest that two mechanisms are involved in the transmitter release induced by nicotine, one dependent on sodium action potentials and the other independent (Trendelenburg, 1965;Su & Bevan, 1970;Jayasundar & Vohra, 1978;Ikushima et al, 1981;1982;Takayanagi et al, 1984;1988;Kizawa & Takayanagi, 1985). In the guineapig detrusor, the contractile response to nicotine seems to be produced mainly through the latter mechanism, and the nicotinic receptors involved are probably located on the nerve terminals rather than on the ganglion cells (Hisayama et al, 1988).…”

“…Nicotine has been reported to induce a tetrodotoxin rabbit and guinea-pig aorta (Ikushima et al, 1981; (TTX)-resistant response in many peripheral organs. 1982), nicotine has been considered to act on presyIn isolated preparations innervated by sympathetic naptic nicotinic receptors (Trendelenburg, 1965;Su nerves, such as rabbit pulmonary artery (Su & 1984;Kizawa et al, 1988;. It has also been reported that nicotine releases tachykinin(s) from chemosensitive sensory nerve in guinea-pig bronchus (Kizawa & Takayanagi, 1985) and rabbit iris sphincter (Hisayama et al, 1988).…”