Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent K⁺channels in coronary arterial smooth muscle cells

Figures

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  Fig. 1. Inhibition of voltage-dependent K+ (Kv) current by escitalopram. Kv currents were recorded by 600-ms depolarizing step pulses from −80 to +60 mV in steps of 10 mV at a holding potential of −80 mV. Representative Kv current in control conditions (A) and in the presence of 10 µM escitalopram (B). (C) Current-voltage (I−V ) relationship at a steady-state Kv current in control conditions (○) and the presence of 10 µM escitalopram (●). n=7. *p<0.05.

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  Fig. 2. Concentration-dependent inhibition of Kv channels by escitalopram. (A) Superimposed current traces obtained by a 600-ms one-step depolarizing pulse of +60 mV from a holding potential of −80 mV in the presence of 0, 0.1, 0.3, 1, 3, 10, 30, and 100 µM escitalopram. (B) Summary of the average concentration-dependent inhibition of Kv currents at steady-state. The percentage inhibition of Kv current is plotted against the various concentrations of escitalopram. All n=6.

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  Fig. 3. Effects of escitalopram on steady-state activation and inactivation curves. (A) Activation curves in the control conditions (○) and in the presence of 10 µM escitalopram (●). Activation curves were obtained by applying short depolarizing (20~50 ms) step pulses between −80 and +60 mV in 10-mV increments at a holding potential of −80 mV, then returned to −40 mV to elicit a tail current. n=7. (B) Inactivation curves in the control conditions (○) and in the presence of 10 µM escitalopram (●). The currents were recorded at a returning pulse of +40 mV after a 7-s preconditioning pulse between −80 and +30 mV. The induced currents were normalized to the peak amplitude of the test potential. n=6.

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  Fig. 4. Effect of Kv 1.5 and/or Kv 2.1 inhibitors on escitalopram-induced inhibition of Kv channels. Current traces were acquired by one-step depolarizing pulses of +60 mV at a holding potential of −80 mV. (A) Representative current traces in the control conditions, in the presence of DPO-1, and in the presence of DPO-1+escitalopram. (B) A summary of these results in (A). n=6. *p<0.05. (C) Representative current traces in the control conditions, in the presence of guangxitoxin, and in the presence of guangxitoxin+escitalopram. (D) A summary of these results in (C). n=5. *p<0.05. (E) Representative current traces in the control conditions, in the presence of DPO-1+guangxitoxin, and in the presence of DPO-1+guangxitoxin+escitalopram. (F) A summary of these results in (E). n=4. *p<0.05.