Gustav Akk, Ph.D.
Molecular Cell Biology Program
Clinical Sciences Research Building (CSRB), Room 5540
GABA, ion channel, neurophysiology, nicotinic receptor, pharmacology, structure-function relations
Function and modulation of transmitter-gated ion channels
My lab is interested in how ligand-gated ion channel work. We focus on the GABAA and nicotinic acetylcholine receptors. The majority of these receptors are located in the postsynaptic cell membrane where they respond to presynaptically released transmitter molecules with a conformational change which results in the flow of ions through the cell membrane. The mechanisms by which agonists and antagonists interact with the ligand-gated ion channels, and how these events lead to conformational changes are critical to our understanding of synaptic transmission and its regulation. Most of the work is carried out on recombinant receptors transiently or stably expressed in a heterologous expression system, such as human embryonic kidney cells or Xenopus oocytes. We utilize an array of electrophysiological approaches: cell-attached and excised single-channel patch clamp, whole-cell and outside-out macroscopic recordings, and two-electrode voltage clamp. We are now establishing a method of simultaneous electrophysiology and fluorescence measurements.
Li P, Bracamontes JR, Manion BD, Mennerick S, Steinbach JH, Evers AS, Akk G. The neurosteroid 5β-pregnan-3α-ol-20-one enhances actions of etomidate as a positive allosteric modulator of α1β2γ2L GABAA receptors. British Journal of Pharmacology, 2014, in press.
Li P, Eaton MM, Steinbach JH, Akk G. The benzodiazepine diazepam potentiates responses of α1β2γ2 γ-aminobutyric acid type A receptors activated by either γ-aminobutyric acid or allosteric agonists. Anesthesiology, 2013, 118:1417-1425.
Akk G, Eaton M, Li P, Zheng S, Lo J, Steinbach JH. Energetic contributions to channel gating of residues in the muscle nicotinic receptor β1 subunit. PLoS One, 2013, 8:e78539.
Eaton MM, Lim YB, Bracamontes J, Steinbach JH, Akk G. Agonist-specific conformational changes in the α1-γ2 subunit interface of the GABAA receptor. Molecular Pharmacology, 2012, 82:255-263.
Li P, McCollum M, Bracamontes J, Steinbach JH, Akk G. Functional characterization of the α5(Asn398) variant associated with risk for nicotine dependence in the α3β4α5 nicotinic receptor. Molecular Pharmacology, 2011, 80:818-827
Li P, Khatri A, Bracamontes J, Weiss DS, Steinbach JH, Akk G. Site-specific fluorescence reveals distinct structural changes induced in the human rho1 GABA receptor by inhibitory neurosteroids. Molecular Pharmacology 2010 77:539-546.
Last Updated: 8/7/2014 9:50:58 AM