DBBS

Ion channels are the molecular units of electrical activity in all cell types, which underlies important physiological functions such as heart contraction and neural activities. My research interests focus on the mechanisms of conformational changes during channel opening and closing and on the interaction of ion channels with other molecules in the cell. Currently, we use a combination of molecular biology, protein biochemistry, patch clamp techniques, and kinetic modeling to study two potassium channels: 1) The BK type calcium-activated potassium channels, which are important in the control of blood pressure 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 IKS channel protein have been shown to cause severe inherited cardiac arrhythmias that often lead to syncope and sudden death. We are interested in how these channels sense cellular signals such as the membrane voltage and intracellular calcium to open, how disease-associated mutations alter channel function, and searching for reagents such as small molecules and peptides that modulate these channels and may lead to drugs for the treatment of human diseases associated with these channels.

Li Y, Zaydman MA, Wu D, Shi J, Guan M, Virgin-Downey BW and Cui J.  KCNE1 enhances PIP2 sensitivity of IKs to modulate channel activity. Proc. Natl. Acad. Sci., U.S.A. 2011 108:9095-9100. PMCID: PMC3107281
 
Wu D, Delaloye K, Zaydman MA, Nekouzadeh A, Rudy Y and Cui J.  State dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation. J. Gen. Physiol. 2010 135:595-606. PMCID: 2888051
 
Lee US, Shi J and Cui J.  Modulation of BK channel gating by the β2 subunit involves both membrane-spanning and cytoplasmic domains of Slo1. J Neurosci. 2010 30:16170-16179. PMCID: 3073600
 
Zhang G, Huang SY, Yang J Shi J, Yang X, Moller A, Zou X and Cui J.  Ion sensing in the RCK1 domain of BK channels. Proc. Natl. Acad. Sci., U.S.A. 2010 107:18700-18705. PMCID: 2972974.
 
Yang J, Krishnamoorthy G, Saxena A, Zhang G, Shi J, Yang H, Delaloye K, Sept D, and Cui J.  An epilepsy/dyskinesia-associated mutation enhances BK channel activation by potentiating the Ca2+ dependent allosteric mechanism. Neuron 2010 66:871-883. PMCID: 2907746 [Previews: Neuron 66, 817-818].
 
Lee US and Cui J.  β subunit-specific modulations of a mutant BK channel associated with epilepsy and dyskinesia. J. Physiol. (London) 2009 587:1481-1498. PMCID: 2678220
 
Yang H, Shi J, Zhang G, Yang J, Delaloye K and Cui J.  Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and the RCK1 domains. Nature Structure and Molecular Biology 2008 15:1152-1159. PMCID: 2579968 [News & Views: Nature Structure and Molecular Biology 15:1130 -1132].
 
Yang H, Hu L, Shi J, Delaloye K, Horrigan F and Cui J.  Mg2+ Mediates Interaction between the Voltage-Sensor and Cytosolic Domain to Activate BK channels. Proc. Natl. Acad. Sci., U.S.A. 2007 104: 18270-18275. PMCID: 2084332 [Commentary: J. Gen. Physiol. 131, 5-11]
 
Hu L, JingyiShi J, Ma Z, Krishnamoorthy G, Sieling F, Zhang G, Horrigan F and Cui J.  Participation of the S4 Voltage Sensor in the Mg2+-Dependent Activation of Large Conductance (BK) K+ Channels. Proc. Natl. Acad. Sci., U.S.A. 2003 100: 10488-10493. PMCID: 193588
 
Shi J, Krishnamoorthy G, Yang Y, Hu L, Chaturvedi N, Harilal D, Qin J and Cui J.  Mechanism of magnesium activation of calcium-activated potassium channels. Nature 2002 418: 876-880.