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.
This molecular study was initiated by positional cloning of the Shaker
voltage-gated potassium channel gene in the fruit fly and expression
cloning of inwardly rectifying potassium channels, founding members
of two large, distantly related families of potassium channels. Mutations
of potassium channels in these 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. A better understanding of potassium channel function 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 genomic--to examine the physiological
functions of potassium channels. |
Ma, D., Zerangue, N. Raab-Graham, K., Fried, S.R., Jan, Y.N., and Jan, L.Y. (2002). Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart. Neuron 33:715-729.
Gu, C., Jan, Y.N., and Jan, L.Y. (2003). A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channel. Science 301:646-649.
Lai, H.C., Grabe, M., Jan, Y.N., and Jan, L.Y. (2005). The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel. Neuron 47:395-406.
Huang, C.S., Shi, S.-H., Ule, J., Ruggiu, M., Barker, L.A., Darnell, R.B., Jan, Y.N., and Jan, L.Y. (2005). Common molecular pathways mediate long-term potentiation of synaptic excitation and slow synaptic inhibition. Cell 123:105-118.
Raab-Graham, K.F., Haddick, P.C.G., Jan, Y.N., and Jan, L.Y. (2006) Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites. Science in press.
information last updated September 2006 |