Effects of articaine on action potential characteristics and the underlying ion currents in canine ventricular myocytes A. Szabó, N. Szentandrássy, P.

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Effects of articaine on action potential characteristics and the underlying ion currents in canine ventricular myocytes A. Szabó, N. Szentandrássy, P. Birinyi, B. Horváth, G. Szabó, T. Bányász, I. Márton, P.P. Nánási, J. Magyar British Journal of Anaesthesia Volume 99, Issue 5, Pages 726-733 (November 2007) DOI: 10.1093/bja/aem263 Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 1 (a) Effect of 100 μM articaine on action potential configuration at a constant pacing frequency of 1 Hz. The first time-derivative of action potential upstroke is shown in the inset. (b, d, and e). Cumulative concentration-dependent effects of articaine on the maximum velocity of depolarization (Vmax), action potential duration measured at 50% (APD50) and 90% (APD90) level of repolarization, and resting membrane potential, respectively. Each concentration of articaine was superfused for 3 min, the washout (WO) lasted for 10 min. Vmax data derived from the experiments in (b) and fitted to the Hill equation are shown in (c). Symbols and bars represent mean (sem) values obtained in five myocytes, asterisks denote significant (P < 0.05) changes from control. British Journal of Anaesthesia 2007 99, 726-733DOI: (10.1093/bja/aem263) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 2 (a and b) Steady-state frequency-dependent effects of 100 μM articaine on Vmax and action potential duration (n = 5). (c and d) Restitution kinetics of Vmax and action potential duration in the absence and presence of 100 μM articaine (n = 6). The solid line in (c) was obtained by exponential fitting to determine the dissociation time constant of articaine from the sodium channel. British Journal of Anaesthesia 2007 99, 726-733DOI: (10.1093/bja/aem263) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 3 Concentration-dependent effects of articaine (from 10 to 1000 μM) on ion currents measured under conventional voltage clamp conditions. (a–e) Left panels show superimposed current traces recorded before and after superfusion with 10, 100, and 1000 μM articaine. ICa, Ito, and IK1 were recorded during the test pulse, while in the case of IKr and IKs the tail currents, obtained upon repolarization, are depicted. Current values were normalized to the cell capacitance. Results fitted to the Hill equation are presented in the right panels, n indicates the number of cells studied. British Journal of Anaesthesia 2007 99, 726-733DOI: (10.1093/bja/aem263) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions

Fig 4 Effects of articaine on ion currents under action potential voltage clamp conditions. Representative records of a command signal (a) and the underlying current traces obtained in the presence of increasing concentrations of articaine (b). The horizontal arrows at left indicate the zero current level for each trace. (c) Suppressive effects of articaine on the inward (representing ICa) and late outward (composed of IK1 + IKr) current peaks. Symbols and bars represent mean (sem) values obtained in four myocytes, asterisks denote significant (P < 0.05) changes from control. British Journal of Anaesthesia 2007 99, 726-733DOI: (10.1093/bja/aem263) Copyright © 2007 British Journal of Anaesthesia Terms and Conditions