Research Abstract:
Ion channels are the molecular units of electrical activity in all cell types. Bioelectricity is generated and modulated as different types of channels open and close in response to various stimuli, such as the binding of a neurotransmitter from outside the cell, a second messenger from inside the cell, or a change in the voltage across the membrane. My research interests focus on the mechanisms underlying conformational changes that occur as the channels open and close and on the interaction of ion channels with other molecules during cellular electrical activity. The approach in our research is to use a combination of molecular biology, protein biochemistry, patch clamp techniques, and biophysical analysis and kinetic modeling. This approach allows us to manipulate channel protein structure, estimate the number of distinct conformational states of the channel protein, and determine the energy associated with the transitions among these states. Current projects involve two potassium channels: 1) The BK type calcium-activated potassium channels, which are important in, among other physiological processes, the control of blood vessel diameter and neurotransmitter release. They are implicated in hypertension and epilepsy; 2) The IKS potassium channels that play a key role in the rhythmic control of the heart rate. Defects in the channel protein have been shown to cause severe inherited cardiac arrhythmias that often lead to syncope and sudden death.
Selected Publications:
Yang H, Hu L, Shi J, et al. Mg2+ Mediates Interaction between the Voltage-Sensor and Cytosolic Domain to Activate BK channels. Proc Natl Acad Sci USA 2007 104:18270-18275.
Hu L, Yang H, Shi J, and Cui J. Effects of multiple metal binding sites on calcium and magnesium-dependent activation of BK channels. J Gen Physiol 2006 127:35-49.
Du W, Bautista J F, Yang H, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet 2005 37:733-738.
Krishnamoorthy G, Shi J, Sept D, and Cui J. The N-terminus of RCK1 domain regulates Ca2+ dependent BKCa channel gating. J Gen Physiol 2005 126:227-241.
Shi J, Krishnamoorthy G, Yang Y, et al. Mechanism of magnesium activation of calcium-activated potassium channels. Nature 2002 418:876-880.
Last Updated: 11/06/2007 |