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- Title
The selective serotonin reuptake inhibitor dapoxetine inhibits voltage-dependent K<sup>+</sup> channels in rabbit coronary arterial smooth muscle cells.
- Authors
Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Sung Eun; Jung, Won‐Kyo; Ha, Kwon‐Soo; Han, Eun‐Taek; Hong, Seok‐Ho; Firth, Amy L; Choi, Il‐Whan; Park, Won Sun
- Abstract
We investigated the inhibitory effect of dapoxetine, a selective serotonin reuptake inhibitor ( SSRI), on voltage-dependent K+ (Kv) channels using native smooth muscle cells from rabbit coronary arteries. Dapoxetine inhibited Kv channel currents in a concentration-dependent manner, with an IC50 value of 2.68±0.94 μmol/L and a slope value (Hill coefficient) of 0.63±0.11. Application of 10 μmol/L dapoxetine accelerated the rate of inactivation of Kv currents. Although dapoxetine did not modify current activation kinetics, it caused a significant negative shift in the inactivation curves. Application of train step (1 or 2 Hz) progressively increased the inhibitory effect of dapoxetine on Kv channels. In addition, the recovery time constant was extended in its presence, suggesting that the longer recovery time constant from inactivation underlies a use-dependent inhibition of the channel. From these results, we conclude that dapoxetine inhibits Kv channels in a dose-, time-, use-, and state (open)-dependent manner, independent of serotonin reuptake inhibition.
- Subjects
INHIBITION of potassium channels; INACTIVATION of potassium channels; SEROTONIN uptake inhibitors; LABORATORY rabbits; CORONARY arteries; PHYSIOLOGY
- Publication
Clinical & Experimental Pharmacology & Physiology, 2017, Vol 44, Issue 4, p480
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12723