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.
Highlights
Primary auditory neurons rely on neurotrophic factors for development and survival
The findings reported demonstrate that combined neurotrophin delivery increases firing latency and action potential duration and induces a small change in the contribution of DTX-I-sensitive currents
There was no change in the total outward potassium current, nor any impact on firing adaptation or entrainment during high frequency pulse trains
Summary
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. These results show that combined BDNF and NT3 exposure influences the contribution of KV1.1 and KV1.2 to the low voltageactivated 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. Given that the clinical application of neurotrophins is guided by the desire to preserve native firing properties, our earlier investigation examined outcomes with combined BDNF and NT36, and determined that firing adaptation was maintained when both neurotrophins were present These findings match those seen in the oculomotor system, where BDNF and NT3 applied individually drive either tonic or phasic firing, but combined exposure maintains the endogenous firing sensitivity[26]. This current is mediated by the family of hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels and has been implicated in setting resting www.nature.com/scientificreports/
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