The selective serotonin reuptake inhibitor dapoxetine inhibits voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
Clin Exp Pharmacol Physiol
; 44(4): 480-487, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-28058743
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Benzylamines
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Selective Serotonin Reuptake Inhibitors
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Coronary Vessels
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Potassium Channels, Voltage-Gated
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Potassium Channel Blockers
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Myocytes, Smooth Muscle
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Naphthalenes
Limits:
Animals
Language:
En
Year:
2017
Type:
Article