K+ channels are key components of the primary and secondary basolateral Cl- pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human K+ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier K+ channel (IKr) in the heart. Mutations in hERG reduce IKr and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to lifethreatening arrhythmias. Paroxetine induced concentrationdependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltageindependent during each voltage pulse. In guinea pig ventricular myocytes held at 36℃, treatment with 0.4 μM paroxetine for 5 min decreased the action potential duration at 90% of repolarization (APD90) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

Introduction
 Materials and Methods
  Ventricular myocyte isolation
  Solutions and action potential recordings frommyocytes
  Expression of hERG in oocytes
  Solution and voltage-clamp recording from oocytes
  Pulse protocols and analysis
  Statistical evaluations
 Results
  Effects of paroxetine on action potentials in guineapig ventricular myocytes
  Concentration-dependence of WT hERG channelblock by paroxetine in Xenopus oocytes
  Voltage-independent block of WT hERG channel byparoxetine
  Time-dependence of WT hERG channel block byparoxetine
 Discussion
 References

• Hee-Kyung Hong(Department of Physiology, Kangwon National University Institute of Bioscience & Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine)
• Soobeen Hwang(Department of Physiology, Kangwon National University Institute of Bioscience & Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine)
• Su-Hyun Jo(Department of Physiology, Kangwon National University Institute of Bioscience & Biotechnology, BK21 plus Graduate Program, Kangwon National University College of Medicine) Correspondence to