Encainide, a class Ic anti-arrhythmic agent, blocks voltage-dependent potassium channels in coronary artery smooth muscle cells

Figures

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  Fig. 1. Effects of encainide on voltage-dependent K+ (Kv) currents in rabbit coronary arterial smooth muscle cells. The Kv currents were recorded using a 600-ms depolarizing pulse from −80 to +60 mV in steps of 10 mV at a holding potential of −80 mV under the control condition (A) and in the presence of 10 μM encainide (B). (C) Summary of the current voltage (I-V) relationship at steady-state Kv currents in the control condition (○) and in the presence of 10 μM encainide (●). n = 6. All n means the number of cells. Only one cell was examined from a rabbit to minimize individual differences. *p < 0.05 (control vs. encainide, at each voltage).

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  Fig. 2. Concentration-dependent inhibition of the voltage-dependent K+ (Kv) channel by encainide. (A) Representative current traces were elicited by 600-ms depolarizing pulses from a holding potential of −80 mV in the presence of 0, 0.1, 0.3, 1, 3, 10, 30, and 100 μM encainide. (B) Concentration-dependent curve for the inhibitory effect of encainide on the Kv current was measured at steady-state (○) and normalized to the current amplitude observed in the absence of encainide (control). Normalized currents were fitted using the Hill equation. n = 6 for all.

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  Fig. 3. Influence of encainide on steady-state activation and inactivation curves. (A) Activation curves under the control conditions (○) and in the presence of 10 μM encainide (●). Activation curves were drawn based on analysis of tail currents, which were induced by applying a short depolarizing step from −80 to +60 mV in 10-mV increments at an −80 mV holding potential, followed by a return potential of −40 mV. The acquired tail currents were normalized to the maximum value of the tail current. n = 6. *p < 0.05 (control vs. encainide, at each voltage). (B) Inactivation curves under the control conditions (○) and in the presence of 10 μM encainide (●). Inactivation curves were obtained by applying a test step to +40 mV after 7-s pre-conditioning at different voltages. The currents induced by the test step were normalized to the peak amplitude of the pre-conditioning step-induced currents. n = 5.

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  Fig. 4. Use (state)-independent effect of encainide on voltage-dependent K+ currents. Twenty repeated depolarizing pulses were applied from a holding potential of −80 mV to +60 mV at frequencies of 1 (A) and 2 (B) Hz in the absence (○) and presence (●) of 10 μM encainide The peak currents were normalized using the peak current recorded after the first pulse and plotted against the pulse number. n = 6.

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  Fig. 5. Roles of Kv1.5 and Kv2.1 subtypes in encainide-induced inhibition of Kv channels. Representative Kv currents were recorded using 600-ms depolarizing steps of +60 mV from a holding potential of −80 mV. (A) Superimposed currents under control conditions and in the presence of 1 μM DPO-1 or 1 μM DPO-1 + 10 μM encainide. (B) Summary of the results shown in panel (A). n = 5. NS, not significant (DPO-1 vs. DPO-1 + encainide). (C) Superimposed currents under control conditions and in the presence of 100 nM guangxitoxin or 100 nM guangxitoxin + 10 μM encainide. (D) Summary of the results shown in panel (C). n = 5. *p < 0.05 (guangxitoxin vs. guangxitoxin + encainide). Kv, voltage-dependent K+.

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  Fig. 6. Effect of encainide on resting membrane potential. (A) Alterations of membrane potential caused by 10 μM encainide. (B) Summary of the effects of encainide on membrane potential. n = 4. *p < 0.05.