1. Local anaesthetic sensitivities of cloned HERG channels from human heart: comparison with HERG/MiRP1 and HERG/MiRP1T8A 
P Friederich, A Solth, S Schillemeit, D Isbrandt 
British Journal of Anaesthesia 
Volume 92, Issue 1, Pages (January 2004)
DOI: /bja/aeh026
Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

2. Fig 1
(a) HERG currents in response to a ramp protocol. Original current traces and the stimulation protocol are shown. Activation of these ion channels by the ramp protocol resulted in a bell-shaped current response. (b) The current densities did not differ between HERG, HERG/MiRP1 and HERG/MiRP1T8A channels expressed in Chinese hamster ovary cells. (c) The currents passing through the channels were quantified as charge flow (area under the current–time curve). Charge flow did not differ between HERG, HERG/MiRP1 and HERG/MiRP1T8A channels. (d) MiRP1 and MiRP1T8A did not influence the time to peak current response of the HERG channels. Data are mean and sd.
British Journal of Anaesthesia  , DOI: ( /bja/aeh026)
Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

3. Fig 2
(a) HERG/MiRP1 currents in response to a ramp protocol followed by a rectangle depolarization. Original current traces and the stimulation protocol are shown. Activation of these ion channels by the additional depolarizing step evoked inactivating outward currents. (b) The current densities of the inactivating outward currents did not differ between HERG, HERG/MiRP1 and HERG/MiRP1T8A channels expressed in Chinese hamster ovary cells. (c) The time course of inactivation of HERG, HERG/MiRP1 and HERG/ MiRP1T8A channels was adequately fitted by a single exponential function. The time constants of channel inactivation did not differ significantly. (d) Current amplitudes evoked by the step depolarization were threefold larger than those evoked by the ramp protocol. MiRP1 and MiRP1T8A did not influence the ratio of peak current responses of the HERG channels. Data are mean and sd.
British Journal of Anaesthesia  , DOI: ( /bja/aeh026)
Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

4. Fig 3
(a) HERG current traces after activation by ramp protocols (shown beneath the current traces). Currents are shown under control conditions and with bupivacaine 30 μM (left), levobupivacaine 10 μM (middle), ropivacaine 25 μM (right), and after wash out. Local anaesthetics reduced the size of the time integrals of current traces (Qramp), inhibited the maximal outward current (Imax) and increased the time needed to reach the peak current. (b) Concentration–response curves for the inhibition of Qramp by bupivacaine, levobupivacaine and ropivacaine. The rank order of potency for the inhibition of Qramp was levobupivacaine > bupivacaine = ropivacaine, with pIC50values of 4.7 M, 5 M and 4.7 M, respectively. (c) The concentration–response curve for the reduction of Qstep by bupivacaine, levobupivacaine and ropivacaine. Local anaesthetics reduced the size of the time integrals of the current traces (Qstep). pIC50values were 4.4 M, 4.5 M and 4.3 M, respectively (see Table 1).
British Journal of Anaesthesia  , DOI: ( /bja/aeh026)
Copyright © 2004 British Journal of Anaesthesia Terms and Conditions

5. Fig 4
(a) HERG/MiRP1T8A current traces after activation by ramp protocols (shown beneath the current traces). Currents are shown under control conditions and with bupivacaine 30 μM (left), levobupivacaine 10 μM (middle), ropivacaine 25 μM (right) and after wash out of the drugs. Local anaesthetics reduced the size of the time integrals of current traces (Qramp), inhibited the maximal outward current (Imax) and increased the time needed to reach peak current. (b) Comparison of inhibition (Qramp) of HERG, HERG/MiRP1 and HERG/MiRP1T8A by bupivacaine 30 μM, levobupivacaine 10 μM and ropivacaine 25 μM. Inhibition of these channel complexes by local anaesthetics was not significantly different between HERG, HERG/MiRP1 and HERG/MiRP1T8A. (c) Comparison of inhibition (Qstep) of HERG, HERG/MiRP1 and HERG/MiRP1T8A by bupivacaine 30 μM, levobupivacaine 10 μM and ropivacaine 25 μM. Inhibition of these channel complexes by all three anaesthetics was not significantly different between HERG, HERG/MiRP1 and HERG/MiRP1T8A.
British Journal of Anaesthesia  , DOI: ( /bja/aeh026)
Copyright © 2004 British Journal of Anaesthesia Terms and Conditions