Modulation of ionic currents in isolated canine and human jejunal circular smooth muscle cells by fluoxetine.
OBJECTIVE
Fluoxetine is a commonly prescribed antidepressant with frequent gastrointestinal side effects. The aim of this study was to examine the effects of fluoxetine on isolated canine and human jejunal circular smooth muscle cells.


METHODS
Patch clamp and dual wavelength ratio techniques were used.


RESULTS
In amphotericin-perforated patch whole-cell recordings, fluoxetine at 100 nmol/L, 1 mumol/L, and 10 mumol/L concentrations decreased the outwardly delayed rectifier potassium current in canine cells by 12% +/- 3%, 27% +/- 12%, and 37% +/- 3%, respectively, and depolarized the membrane potential by 9.7 +/- 1.8 mV at 10 mumol/L. At 100 mumol/L and 1 mmol/L concentrations, fluoxetine increased the outward current by 88% +/- 40% and 475% +/- 270%, respectively. The increase in the outward current was blocked by charybdotoxin, suggesting an effect on the calcium-activated potassium current. In human cells, fluoxetine at 1 mumol/L decreased the outward potassium current by 26% +/- 4% and at 100 mumol/L increased the outward potassium current by 134% +/- 22%.


CONCLUSIONS
Fluoxetine had direct effects on canine and human jejunal circular smooth muscle cells. Low concentrations decreased the outwardly delayed rectifier potassium current, and higher concentrations activated calcium-activated potassium channels. The results may in part explain the frequent gastrointestinal side effects of the drug.
Farrugia
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Division of Gastroenterology and Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002478:Cells, Cultured; D004285:Dogs; D004560:Electricity; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007583:Jejunum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D015221:Potassium Channels; D017367:Selective Serotonin Reuptake Inhibitors