title: Firing frequency and entrainment maintained in primary auditory neurons in the presence of combined BDNF and NT3.
abstract: Primary auditory neurons rely on neurotrophic factors for development and survival. We previously determined that exposure to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) alters the activity of hyperpolarization-activated currents (Ih) in this neuronal population. Since potassium channels are sensitive to neurotrophins, and changes in Ih are often accompanied by a shift in voltage-gated potassium currents (IK), this study examined IK with exposure to both BDNF and NT3 and the impact on firing entrainment during high frequency pulse trains. Whole-cell patch-clamp recordings revealed significant changes in action potential latency and duration, but no change in firing adaptation or total outward IK. Dendrotoxin-I (DTX-I), targeting voltage-gated potassium channel subunits KV1.1 and KV1.2, uncovered an increase in the contribution of DTX-I sensitive currents with exposure to neurotrophins. No difference in Phrixotoxin-1 (PaTX-1) sensitive currents, mediated by KV4.2 and KV4.3 subunits, was observed. Further, no difference was seen in firing entrainment. These results show that combined BDNF and NT3 exposure influences the contribution of KV1.1 and KV1.2 to the low voltage-activated potassium current (IKL). Whilst this is accompanied by a shift in spike latency and duration, both firing frequency and entrainment to high frequency pulse trains are preserved.
authors.affiliation: Department of Surgery (Otolaryngology), University of Melbourne, Royal Victorian Eye &Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Tess
authors.initials: T
authors.lastname: Wright
authors.affiliation: Bionics Institute, East Melbourne, Victoria, Australia.|Office for Research Ethics and Integrity, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Gillespie
authors.affiliation: Department of Surgery (Otolaryngology), University of Melbourne, Royal Victorian Eye &Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Leary
authors.affiliation: Department of Surgery (Otolaryngology), University of Melbourne, Royal Victorian Eye &Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Karina
authors.initials: K
authors.lastname: Needham
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004546:Elapid Venoms / Q000494:pharmacology; D051662:Kv1.1 Potassium Channel / Q000378:metabolism; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004546:Elapid Venoms; D051663:Kv1.2 Potassium Channel; D020933:Neurotrophin 3; D024642:Potassium Channels, Voltage-Gated; C108582:dendrotoxin I; D051662:Kv1.1 Potassium Channel; D011188:Potassium