Among the environmental chemicals that may be able to disrupt the endocrine systems of animals and humans are polychlorinated biphenyls (PCBs), a chemical class of considerable concern. PCB consists of two six-carbon rings linked by a single carbon bond, and theoretically, 209 congeners can form, depending on the number of chlorines and their location on the biphenyl rings. Furthermore, 3,3’,4,4’,5-pentachlorobiphenyl (PCB126) exposure also increases nitric oxide production and nuclear factor kappa-light-chain-enhancer of activated B cells binding activity in chondrocytes, thus contributing as an initiator of chondrocyte apoptosis and resulting in thymic atrophy and immunosuppression. This study identified whether cardiac and immune abnormalities from PCB126 were caused by the Kv1.3 and Kv1.5 channels. PCB126 did not affect either the steady-state current or peak current of the Kv1.3 and Kv1.5 channels. However, PCB126 right-shifted the steady-state activation curves of human Kv1.3 channels. These results suggest that PCBs can affect the heart in a way that does not block voltage-dependent potassium channels including Kv1.3 and Kv1.5 directly.

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.