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The effects of synthetic poneratoxin (PoTX), a new toxin isolated from the venom of the ant Paraponera clavata, were studied under current- and voltage-clamp conditions in frog skeletal muscle fibres. PoTX induces a concentration-dependent (10(-9) M-5 x 10(-6) M) prolongation of the action potentials and, at saturating concentration, a slow repetitive activity developing at negative potentials. PoTX specifically acts on voltage-dependent Na channels by decreasing the peak Na current (INa) and by simultaneously inducing a slow INa which starts to activate at -85 mV and inactivates very slowly. Both the fast and the slow components of INa are suppressed by tetrodotoxin and reverse at the same potential corresponding to the equilibrium potential for Na ions. The fast component of INa has voltage dependence, activation and steady-state inactivation almost similar to those of the control INa. The voltage dependence of the slow Na conductance is 40 mV more negative than that of the fast one. The results suggest that PoTX affects all the Na channels and that the fast and the slow INa components originate from a possible PoTX-induced interconversion between a fast and a slow operating mode of the Na channels.

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