PD Dr. Dr. Tobias Huth

Properties and Functions of Na+ and K+ Channels and their regulation by BACE1. Physiological functions of BACE1 (group leader: Tobias Huth)

Using brain slices, acutely isolated neurons and heterologous expression systems, we are investigating properties and functions of voltage-dependent Na+ and K+ currents. In particular, we are studying how these currents are modulated by the β-site APP cleaving enzyme 1 (BACE1). In the context of these studies, we aim at identifying physiological functions of BACE1 besides its crucial role in the amyloid cascade hypothesis of Alzheimer´s disease.

Selected publications:

• • Alzheimer C, Schwindt PC and Crill WE: Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat neocortex. J Neurosci 13: 660-673, 1993
  • Lipowsky R, Gillessen T and Alzheimer C: Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells. J Neurophysiol 76: 2181-2191, 1996.
  • Takigawa T and Alzheimer C: G protein-activated inwardly rectifying K+ (GIRK) currents in dendrites of rat neocortical pyramidal cells. J Physiol (Lond.) 517:385-390, 1999.
  • Huth T, Schmidt-Neuenfeldt K, Rittger A, Saftig P, Reiss K, Alzheimer C. Non-proteolytic effect of ß-site APP- cleaving enzyme 1 (BACE1) on sodium channel function. Neurobiol Dis 33: 282-289, 2009.
  • Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, Alzheimer C, Grafe P, Carr RW. Anti-cancer drug oxaliplatin induces acute cooling-aggravated neuropathy via Nav1.6-mediated resurgent and persistent current. Proc Natl Acad Sci (USA) 109:6704-6709, 2012.
  • Hessler S, Zheng F, Hartmann S, Rittger A, Lehnert S, Völkel M, Nissen M, Edelmann E, Saftig P, Schwake M, Huth T, Alzheimer C. β-secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion. J Neurosci 35: 3298-3311, 2015.
  • Hartmann S, Zheng F, Kyncl M, Karch S, Voelkl K, Zott B, D’Avanzo C, Lomoio S, Tesco G, Kim DY*, Alzheimer C, Huth T. β-Secretase BACE1 promotes surface expression and function of Kv3.4 at hippocampal mossy fiber synapses. J Neurosci 38: 3480-3494, 2018
  • Dierich M, Hartmann S, Dietrich N, Moeser P, Brede F, Johnson Chacko L, Tziridis K, Schilling A, Krauss P, Hessler S, Karch S, Schrott-Fischer A, Blumer M, Birchmeier C, Oliver D, Moser T, Schulze H, Alzheimer C, Leitner M, Huth T. β-secretase BACE1 is required for normal cochlear function. J Neurosci 39: 9013-9027, 2019