GIRK channels (or Kir3 channels) are known to play diverse roles including important regulation of cardiac, neuronal, and endocrine physiology.28 e rst known eect of GIRK channels was their role in underlying IKACh, the cardiac current largely responsible for the

negative chronotropic eects of vagally released ACh. e inhibitory action of the vagus nerve on the heart has been demonstrated since at least the nineteenth century when the brothers Eduard and Ernst Weber communicated their results to an Italian congress of scientists in 1845.20,38 ey showed that heart rate in a frog preparation could be slowed and brought to a stop by stimulation of the vagus nerves using a rotary galvano-magnetic apparatus. e sensitivity of this vagal inhibition to atropine and its accompaniment by the hyperpolarization of the heart muscle were recognized as early as 1886 by Gaskell using extracellular recordings.21,22 Furthermore, through careful chemical quantitation of extracellular uids, Howell and Duke had demonstrated by 1908 that vagal inhibition of the heart is accompanied by a small release of potassium.29