Effects of New World scorpion toxins on single-channel and whole cell cardiac sodium currents

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Abstract
Purified toxins from a North American scorpion, Centruroides noxius (Cn II-10), and a South American scorpion, Tityus serulatus (Ts-.gamma.), were tested on cardiac sodium channels using patch-clamp methods to record whole cell and single-channel currents. The two toxins produced similar effects on sodium currents; potassium and calcium currents were not affected. Macroscopic sodium current amplitudes, measured at test potentials > -20 mV where the opening probability was high, decreased in a concentration-dependent manner with a half maximum inhibitory concentration of 6 .times. 10-8 M. Block was unchanged by repetitive depolarizing pulses. In the presence of scorpion toxin, the currents were rapidly blocked by tetrodotoxin (3 .times. 10-5 M). Both toxins shifted the voltage dependence of sodium channel inactivation to more negative potentials. At test potentials between -50 and -70 mV, where the sodium channel opening probability is normally low, both toxins produced an increase in sodium current and slowed the rates of activation and inactivation. At intermediate potentials between -50 and -20 mV the currents. At a test potential of -20 mV, the toxins decreased single-channel activity and increased the latency to first opening. At a test potential of -60 mV, the toxins significantly prolonged channel open time. The unitary current amplitudes were unchanged at either potential. We conclude that New World scorpion toxins produce apparently complex effects on whole cell currents primarily by retarding activation gating of cardiac sodium channels.

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