Christopher J. Lingle, Ph.D.

Professor
Anesthesiology
Neuroscience

Biochemistry, Biophysics, and Structural Biology Program
Neurosciences Program

  • 314-362-8558

  • 314-362-8559

  • 314-362-8571

  • 5552 Clinical Sciences Research Building

  • clingle@morpheus.wustl.edu

  • http://elysium.wustl.edu/LingleLab/

  • ion channel, protein structure, neurobiology, physiology, cell signaling

  • Structure-function studies of Slo family K+ channels

Research Abstract:

We use biophysical, biochemical, and genetic methods to investigate the functional properties of a family of large-conductance K+ ion channels which are regulated by soluble cytosolic factors. This family includes the widely-distributed BK channel that is regulated by cytosolic Ca2+ and membrane voltage and other family members regulated by cytosolic pH (Slo3) and cytosolic Na+ (Slo2.1 and Slo2.2). Using biophysical approaches coupled with mutational manipulations of the channel genes, we study the underlying mechanisms by which the ion channels are allosterically regulated by ligand and voltage. We also pursue topics concerned with regulation by auxiliary subunits. Finally, we use genetic approaches to delete relevant subunits from in mouse tissues to allow us to address questions concerned with the physiological role of channel subunits. Behavioral studies are employed to assess potential phenotypic consequences of gene deletion.

Selected Publications:

Gonzalez-Perez V, Zeng X-H, Henzler-Wildman K, and Lingle CJ. Stereospecific binding of a disordered peptide segment mediates BK channel inactivation. Nature 2012; 485:133-136. PMID:22522931

Yang C, Zeng X-H, Zhou Y, Xia X-M and Lingle CJ. LRRC52, a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel. PNAS 2011 108:19419-19424. PMID:22084117

Zhou Y, Xia X-M and Lingle CJ. Cysteine scanning and modification reveal major differences between BK channels and Kv channels in the inner pore region. Proc. Natl. Acad. Sci. USA. 2011 108:12161-12166. PMID: 21730134

Zeng X-H, Yang C, Kim S-T, Lingle CJ and Xia X-M. Deletion of the Slo3 gene abolishes alkalization-activated K+ current in mouse spermatozoa. Proc. Natl. Acad. Sci. USA. 2011 108:5879-5884. PMID:21427226

Zhou Y, Tang Q-Y, Xia X-M and Lingle CJ. Glycine311, a determinant of paxilline block in BK channels: a novel bend in the BK S6 helix. Journal of General Physiology 2010 135:481-494. PMID:20421373

Zeng X-H, Benzinger GR, Xia X-M and Lingle CJ. BK channels with 3a subunits generate use-dependent slow afterhyperpolarizing currents by an inactivation-coupled mechanism. Journal of Neuroscience 2007 27:4707-4715. PMID:17460083

Chen X-K, Wang L-C, Zhou Y, Cai Q, Prakriya M, Duan K-L, Sheng Z-H, Lingle C and Zhuo Z. Activation of GPCRs modulates quantal size in chromaffin cells through G(betagamma) and PKC. Nature Neuroscience 2005 8:1160-1168. PMID:16116443

Xia X-M, Zhang X and Lingle CJ. Ligand-dependent activation of Slo family channels is defined by interchangeable cytosolic domains. Journal of Neuroscience 2004 24:5585-5591. PMID:15201331

Zeng X, Xia X-M and Lingle CJ. Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels. Nature Structural Biology 2003 10:448-454. PMID:12740608

Xia X-M, Zeng X and Lingle CJ. Multiple regulatory sites in large-conductance calcium-activated potassium channels. Nature 2002 418:880-884. PMID:12192411

Last Updated: 7/29/2013 2:41:02 PM

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