Korean J Physiol Pharmacol.  2017 Jul;21(4):415-421. 10.4196/kjpp.2017.21.4.415.

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

• Kim HS
• Li H
• Kim HW
• Shin SE
• Seo MS
• An JR
• Ha KS
• Han ET
• Hong SH
• Choi IW
• Choi G
• Lee DS
• Park WS

• KMID: 2384455
• DOI: http://doi.org/10.4196/kjpp.2017.21.4.415

Abstract

We investigated the inhibitory effect of escitalopram, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K⁺ (Kv) channels in freshly separated from rabbit coronary arterial smooth muscle cells. The application of escitalopram rapidly inhibited vascular Kv channels. Kv currents were progressively inhibited by an increase in the concentrations of escitalopram, suggesting that escitalopram inhibited vascular Kv currents in a concentration-dependent manner. The ICâ‚…â‚€ value and Hill coefficient for escitalopram-induced inhibition of Kv channels were 9.54±1.33 µM and 0.75±0.10, respectively. Addition of escitalopram did not alter the steady-state activation and inactivation curves, suggesting that the voltage sensors of the channels were not affected. Pretreatment with inhibitors of Kv1.5 and/or Kv2.1 did not affect the inhibitory action of escitalopram on vascular Kv channels. From these results, we concluded that escitalopram decreased the vascular Kv current in a concentration-dependent manner, independent of serotonin reuptake inhibition.

Keyword

Coronary artery; Escitalopram; Serotonin reuptake inhibition; Smooth muscle; Voltage-dependent K⁺ channel

MeSH Terms

Citalopram*
Coronary Vessels
Muscle, Smooth*
Myocytes, Smooth Muscle*
Serotonin*
Citalopram
Serotonin

Figure

• 

  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.

• 

  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.

• 

  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.

• 

  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.

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