Chloroform is a potent activator of cardiac and neuronal Kir3 channels

Chloroform has been used over decades in anesthesia before it was replaced by other volatile anesthetics like halothane or sevoflurane. Some of the reasons were inadmissible side effects of chloroform like bradycardia or neural illness. In the present study, we identified members of the G protein-activated inwardly rectifying potassium channel family (Kir3) expressed in Xenopus oocytes as potential common molecular targets for both the neural and cardiac effects of chloroform. Millimolar concentration currents representing a 1:10000 dilution of commercially available chloroform were used in laboratories that augment neuronal Kir3.1/3.2 currents as well as cardiac Kir3.1/3.4. This effect was selective and only observed in currents from Kir3 subunits but not in currents from Kir2 subunits. Augmentation of atrial Kir3.1/3.4 currents leads to an effective drop of the heart rate and a reduction in contraction force in isolated mouse atria.