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The effects of local anaesthetics and holding potential on sodium and asymmetry currents were studied in intracellularly dialysed squid giant axons. The asymmetry currents were fractionated into their inactivating and non-inactivating components, and the charge displacements Qi and Qn of the two components were determined for pulse potentials between -20 and +40 mV. The charged local anaesthetic RAD 366, a quaternary derivative of lidocaine, applied internally at a concentration in the dialysis solution of 1 mM, did not change Qn, but reduced Qi about 3-fold. The neutral local anaesthetic benzocaine, applied externally at a concentration in the bathing solution of 1 mM, had effects very similar to RAD 366. It did not change Qn, but reduced Qi and the sodium current about 2 . 5-fold. Unlike local anaesthetics, steady membrane depolarization had essentially equal effects on Qn, Qi and sodium current. Lowering the holding potential from -98 to -60 mV for several minutes reduced all three variables to about half. Models of sodium channel voltage-gating are discussed which implicate both Qn and Qi, and which account for the selective blockage of Qi by sodium inactivation and local anaesthetics.

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				M. F. Sheets and D. A. Hanck Molecular Action of Lidocaine on the Voltage Sensors of Sodium Channels J. Gen. Physiol., February 3, 2003; 121(2): 163 - 175. [Abstract] [Full Text] [PDF]