Potassium Channel Research May Shed Light on Heart Ailment

Release Date:
3/28/2000
Contact:

In order to function, many of our cells--including those in our heart, brain, and digestive tract--need to control the flow of potassium across their membranes. This flow is regulated by channel proteins--literally proteins that form channels through cellular membranes. Potassium ions flow freely into or out of cells when the channels are open. The channels open and close in response to biochemical stimuli.

In FY 1998, a team of researchers lead by Dr. Roderick MacKinnon of The Rockefeller University got a closer look at these potassium channels. Using X-ray crystallography, the scientists were able to determine the three-dimensional structure of a potassium channel molecule. In FY 1999, Dr. MacKinnon's group examined the chemical properties of the molecule.

Potassium Channel

Model of a potassium channel molecule from a bacterium. This top view of the molecule shows a potassium ion (black dot) positioned inside the pore. Dr. MacKinnon's group expects that potassium channels in all organisms will share this same molecular architecture.

Based on the simple principle that ions, such as potassium, are normally repelled from the oily membrane of cells, the researchers asked: How does this channel protein allow potassium ions to cross the membrane? They knew from their earlier research that, to accommodate the water-loving potassium ions that pass through it, the channel protein actually maintains a watery environment at its core. Their latest studies showed that the electrical properties of the protein's center are perfectly tuned for the potassium ion.

Recently, the researchers also determined the structure of a separate section of the potassium channel, called the beta subunit. This part of the channel is not inserted through the membrane, but lies inside the cell, in contact with the rest of the channel protein. It is thought to help control the chemistry of the cell, which is linked with the opening and closing of the channel.

Finally, the scientists determined part of the structure of a specialized potassium channel that helps regulate heart rhythm. Defective versions of this channel underlie one form of long QT syndrome, a genetic condition that causes irregular heartbeat and sudden death.

Potassium channels are critical for many bodily functions, including heartbeat, nerve signaling, digestion, and insulin release. A better understanding of potassium channels may help scientists develop drugs to treat diseases ranging from heart ailments to diabetes.

REFERENCES

Roux B, MacKinnon R. The cavity and pore helices in the KscA K + channel: Electrostatic stabilization of monovalent cations. Science 1999;285:100-2.

Gulbis JM, Mann S, MacKinnon R. Structure of a voltage-dependent K + channel subunit. Cell 1999;97:943-52.

Cabral JHM, Lee A, Cohen SL, Chait BT, Li M, MacKinnon R. Crystal structure and functional analysis of the HERG potassium channel N terminus: A eukaryotic PAS domain. Cell 1998;95:649-55.

Reporters may call the NIGMS Office of Communications and Public Liaison​ at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Cell Biology and Biophysics who can comment on this work.