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Martin Wallner, Ph.D.

Work Email Address:
mwallner@mednet.ucla.edu

Work Phone Number:
310-825-5748



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Department / Division Affiliations
Member, Brain Research Institute

Research Interest:

Physiology and pharmacology of GABA(A) receptors, the main inhibitory neurotransmitter receptors in mammalian brain

Dr. Wallner's research focuses on the physiology and pharmacology of GABA(A) receptors, the main inhibitory neurotransmitter receptors in mammalian brain. Drugs that activate GABA(A) receptor subtypes lead to sedation, anesthesia, anxiolysis and sleep, and are used to treat hyperexcitability disorders like epilepsy and insomnia. Our particular interest is centered on a unique form of non-synaptic inhibitory action mediated by highly GABA-sensitive extrasynaptic GABA(A) receptor subtypes that show constant (tonic) activity. These type of GABA receptors are not only highly sensitive to relevant low alcohol concentrations, but also to other intoxicating drugs like muscimol, the psychoactive ingredient in the mushroom amanita muscaria. We have collected evidence that these extrasynaptic GABA(A) receptor subtypes are, in part, responsible for many of the well-known effects of alcohol intoxication. Particularly intriguing the discovery that behavioral benzodiazepine alcohol antagonists (e.g., Ro15-4513) are competitive alcohol antagonist on extrasynaptic subtypes (?4/6?3?) GABA(A) receptors. This work opens the opportunity for new drugs that target this alcohol GABA(A) receptor site in our brain. Such drugs may include novel alcohol antagonists, but perhaps even more promising might be potential alcohol agonists (mimetics) that harness specific beneficial effects of alcohol. Further interests are the potential involvement of extrasynaptic GABA(A) receptor in the physiology and pharmacology of sleep as well as the role such alcohol-sensitive GABA(A) receptors might in play in alcohol reward and addiction.

Publications:

Meera Pratap, Olsen Richard W, Otis Thomas S, Wallner Martin Etomidate, propofol and the neurosteroid THDOC increase the GABA efficacy of recombinant alpha4beta3delta and alpha4beta3 GABA A receptors expressed in HEK cells. Neuropharmacology. 2009; 56(1): 155-60.
Wallner M, Olsen R W Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development?. Br. J. Pharmacol. 2008; 154(2): 288-98.
Santhakumar Vijayalakshmi, Wallner Martin, Otis Thomas S Ethanol acts directly on extrasynaptic subtypes of GABAA receptors to increase tonic inhibition. Alcohol. 2007; 41(3): 211-21.
Wallner Martin, Hanchar H Jacob, Olsen Richard W Low dose acute alcohol effects on GABA A receptor subtypes. Pharmacol. Ther. 2006; 112(2): 513-28.
Hanchar H Jacob, Chutsrinopkun Panida, Meera Pratap, Supavilai Porntip, Sieghart Werner, Wallner Martin, Olsen Richard W Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors. Proc. Natl. Acad. Sci. U.S.A. 2006; 103(22): 8546-51.
Wallner M, Hanchar H J, Olsen R W Low-dose alcohol actions on alpha4beta3delta GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513. Proc. Natl. Acad. Sci. U.S.A. 2006; 103(22): 8540-5.
Hanchar H Jacob, Dodson Paul D, Olsen Richard W, Otis Thomas S, Wallner Martin Alcohol-induced motor impairment caused by increased extrasynaptic GABA(A) receptor activity. Nat. Neurosci. 2005; 8(3): 339-45.
Wallner M, Hanchar H J, Olsen R W Ethanol enhances alpha 4 beta 3 delta and alpha 6 beta 3 delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans. Proc. Natl. Acad. Sci. U.S.A. 2003; 100(25): 15218-23.
Meera P, Wallner M, Toro L A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc. Natl. Acad. Sci. U.S.A. 2000; 97(10): 5562-7.
Wallner M, Meera P, Toro L Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog. Proc. Natl. Acad. Sci. U.S.A. 1999; 96(7): 4137-42.
Meera P, Wallner M, Song M, Toro L Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc. Natl. Acad. Sci. U.S.A. 1997; 94(25): 14066-71.
Wallner M, Meera P, Toro L Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus. Proc. Natl. Acad. Sci. U.S.A. 1996; 93(25): 14922-7.
Wallner M, Weigl L, Meera P, Lotan I Modulation of the skeletal muscle sodium channel alpha-subunit by the beta 1-subunit. FEBS Lett. 1993; 336(3): 535-9.