Northwestern Events Calendar

Dec
2
2019

Direct Activation of Potassium Channels by Neurotransmitters and Ancient Medicines

When: Monday, December 2, 2019
4:00 PM - 5:00 PM  

Where: Ward Building, Room 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Public - Post Docs/Docs - Graduate Students

Contact: Lexi Nash   312.503.4893

Group: Department of Pharmacology Seminars

Category: Lectures & Meetings

Description:

Geoffrey W. Abbott, Ph.D.
Professor of Pharmacology, Physiology and Biophysics
University of California – Irvine

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in vertebrate CNS.  The canonical action of GABA is via binding to neuronal GABA receptors (GABARs) to induce hyperpolarization by intrinsic (GABAA/CRs) or extrinsic (GABABRs) ion channel activation.  Voltage-gated potassium channels KCNQ2-5, especially KCNQ2/3 heteromers, generate the neuronal M-current, another important hyperpolarizing force.  Here, we discuss our recent finding that GABA and related metabolites directly activate KCNQ2/3 channels, and KCNQ2/3-dependently hyperpolarizes cells, with sensitivity comparable to the most sensitive α/β/γ GABAARs.  We identified the M-channel GABA binding site as KCNQ3-W265, a position conserved for >500 million years in deuterostome clades but absent in protostomes and in cardiac-expressed KCNQ1.  M-channel activation is a novel, unexpected mechanism for physiological and therapeutic inhibitory actions of GABA and analogues.  This work has led to further discoveries in KCNQ channel pharmacology, including isolation of a potent KCNQ channel activator from cilantro.  We also found that activation of the vascular-expressed KCNQ5 is a common mechanism for a variety of genetically and culturally diverse hypotensive botanical folk medicines. The implications of this work will be discussed with respect to KCNQ channel physiology, pharmacology and drug discovery.  

Add to Calendar

Add Event To My Group:

Please sign-in