Gustav Akk

Effects of ivermectin on the activation and desensitization of the human GABAA receptor

Spencer Pierce, Allison L. Germann, Ka Tak Tsoi, Gustav Akk

Ivermectin is a widely-used antiparasitic drug that acts through allosteric activation and potentiation of the glutamate-gated chloride channel present in neurons and muscle cells of helminths and insects.In mammals, ivermectin activates several members of the Cys-loop ion channel family including the GABA …

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Activation of the human β3 GABAA receptor by combinations of receptor protonation with chemical agonists and gain-of-function mutations

Allison L. Germann, Spencer R. Pierce, Joe Henry Steinbach, Gustav Akk

Native GABA A receptors are continuously exposed to numerous active compounds, including protons, whose net activating and modulatory effects determine receptor function and underlie the inhibitory tone in the brain. Here, we have investigated the interactions and energetic additivity between activation of …

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The relationship between apparent potentiation and the magnitude of the control response

Joe Henry Steinbach, Gustav Akk

The effect of a potentiating drug on ion channel function is typically evaluated by comparing current responses to the control agonist in the presence and absence of the potentiator. Differences in ratios of responses are then taken as proof of distinct potentiation …

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Properties of Acute Activation and Inhibition of the β3 Homomeric GABAA Receptor Mediated by Protonation of Conserved Histidine Residues

Spencer R. Pierce, Allison L. Germann, Yu Zhou, Saumith L. Menon et autres

GABA A receptors are inhibitory transmitter-gated ion channels formed of various combinations of the 19 homologous subunits cloned to date. Changes in extracellular pH have been shown to directly activate the receptor or modulate its activity elicited by a chemical agonist, but …

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BPS2025 - Differential binding and action of neurosteroids in β3-homopentameric GABAA receptor

Satoshi Koyama, Zhihui He, John Bracamontes, Gustav Akk et autres

Null method to estimate the maximal PA at subsaturating concentrations of agonist

Allison L. Germann, Steven R. Pierce, Joe Henry Steinbach, Gustav Akk

The maximal probability of being in an active state (PA,max) is a measure of gating efficacy for a given agonist acting on a given receptor channel. In macroscopic electrophysiological recordings, PA,max is typically estimated by comparing the amplitude of the current response …

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Stereospecific Properties and Intracellular Transport of Novel Intrinsically Fluorescent Neurosteroids

Vibeke Akkerman, Peter Reinholdt, Rasmus Schnoor-Madsen, Line Lauritsen et autres

Allopregnanolone (AlloP) is an example of neuroactive steroids (NAS), which is a potent allosteric activator of the γ-aminobutyric acid A (GABA A ) receptor. The mechanisms underlying the biological activity of AlloP and other NAS are only partially understood. Here, we present …

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Author Correction: AI is a viable alternative to high throughput screening: a 318-target study

Izhar Wallach, Denzil Bernard, Kong T. Nguyen, Gregory Ho et autres

As a result, the correct Affiliation for Andrew B. Herr, Benjamin Liou, David A. Hildeman, Joseph J. Maciag, Ying Sun, Durga Krishnamurthy, and Stephen N. Waggoner is:

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Three classes of propofol binding sites on GABAA receptors

Zi-Wei Chen, Satyanarayana M. Chintala, John Bracamontes, Yusuke Sugasawa et autres

Propofol is a widely used anesthetic and sedative that acts as a positive allosteric modulator of gamma-aminobutyric acid type A (GABA A ) receptors. Several potential propofol binding sites that may mediate this effect have been identified using propofol-analogue photoaffinity labeling. Ortho-propofol …

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Inhibitory Actions of Potentiating Neuroactive Steroids in the Human α1β3γ2L γ-Aminobutyric Acid Type A Receptor

Spencer R. Pierce, Allison L. Germann, Douglas F. Covey, Alex S. Evers et autres

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Direct measurements of neurosteroid binding to specific sites on GABAA receptors

Satyanarayana M. Chintala, Hiroki Tateiwa, Mingxing Qian, Yuanjian Xu et autres

Abstract Background and Purpose Neurosteroids are allosteric modulators of GABAA currents, acting through several functional binding sites although their affinity and specificity for each site are unknown. The goal of this study was to measure steady‐state binding affinities of various neurosteroids for …

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Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABAA receptor and CaV2.2 channel

Han‐Shen Tae, Marcelo O. Ortells, Arsalan Yousuf, Sophia Q. Xu et autres

In this study, we have investigated the pharmacological activity and structural interaction of two novel psychoplastogens, tabernanthalog (TBG) and ibogainalog (IBG) at heterologously-expressed rat (r) and human (h) nicotinic acetylcholine receptors (nAChRs), the rα1β2γ2L γ-aminobutyric acid type A receptor (GABAAR), and the …

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