Electrical Signaling

Potassium channels are proteins which selectively allow potassium ions to exit the cell down their chemical gradient. These molecules, along with sodium channels, are pivotal for generating the electrical signals that excitable cells utilize to send intercellular signals at very high speeds. Both potassium and sodium channels which comprise the primary "legs" for this signaling process are voltage-gated, meaning changes in the resting membrane potential activate them. Other ion-selective channel families involved in this electrical signaling are calcium and chloride channels, many of which are voltage-gated. Sodium channels propagate the electrical signal by opening and allowing an inward flux of sodium ions, while potassium channels end the signal by repolarizing the membrane. Hence, they often act as a brake by damping the electrical signal.

We have been studying the Kv7 family of potassium channels now for several years. The family has clear connections to many genetic diseases long QT syndrome, a cardiac pathology, and epilepsy. When the mutant genes, which encode mutated protein channels are expressed they are often not functional or are faulty.

The Kv7.1 tetramerization module, which assists proper channel assembly in the cell, is depicted on the background of an electrocardiogram trace. In order to form a working channel, four subunits assemble together.

Our work has focused on Kv7 channels, also known as KCNQ, which is an integral membrane protein that has a large intracellular domain. Calmodulin, the ubiquitous Ca2+ sensor protein shown in pink, binds to this intracellular domain, acting as a molecule chaperone for the channel. It also appears to play a role in channel gating. Depicted is a molecular model for this channel complex based on experimental and computational studies.