Lily Jan, Ph.D.
Potassium channels regulate neuronal signaling, control the flow of salt across epithelia, heart rate, vascular tone, and the release of hormones such as insulin, and protect neurons and muscles under metabolic stress. In order to study potassium channels, we have chosen to isolate individual potassium channel genes so that the channels they give rise to can be studied one at a time, and then compared with potassium channels in native tissues. We have recently extended our studies to the cloning and characterization of calcium-activated chloride channels with wide distribution and diverse physiological functions.
Thus our channel studies were initiated by positional cloning of the Shaker voltage-gated potassium (Kv) channel gene in the fruit fly and expression cloning of inwardly rectifying potassium (Kir) channels - founding members of two large, distantly related families of potassium channels - as well as expression cloning of calcium-activated chloride channel (CaCC) of a novel ion channel family. Mutations of potassium channels in the Kv and Kir families cause diseases of the brain (epilepsy, episodic ataxia), ear (deafness), kidney (hypertension), pancreas (hyperinsulinemic hypoglycemia of infancy), heart (arrhythmia), skeletal muscle (periodic paralysis), as well as developmental abnormalities of neural crest-derived tissues (Andersen's syndrome). Understandably, potassium channel openers and blockers have been developed for pharmaceutical purposes. Likewise, CaCC blockers may reduce hypertension whereas CaCC enhancement has been considered as potential treatment for cystic fibrosis and other pulmonary diseases including asthma. A better understanding of the function of these channels will therefore not only satisfy our curiosity, it will have clinical significance. We are currently taking a range of experimental approaches - electrophysiological, cell biological, biochemical and genetic - to examine the physiological functions of potassium channels and calcium-activated chloride channels.