title: Presynaptic resurgent Na+ currents sculpt the action potential waveform and increase firing reliability at a CNS nerve terminal.
abstract: Axonal and nerve terminal action potentials often display a depolarizing after potential (DAP). However, the underlying mechanism that generates the DAP, and its impact on firing patterns, are poorly understood at axon terminals. Here, we find that at calyx of Held nerve terminals in the rat auditory brainstem the DAP is blocked by low doses of externally applied TTX or by the internal dialysis of low doses of lidocaine analog QX-314. The DAP is thus generated by a voltage-dependent Na(+) conductance present after the action potential spike. Voltage-clamp recordings from the calyx terminal revealed the expression of a resurgent Na(+) current (I(NaR)), the amplitude of which increased during early postnatal development. The calyx of Held also expresses a persistent Na(+) current (I(NaP)), but measurements of calyx I(NaP) together with computer modeling indicate that the fast deactivation time constant of I(NaP) minimizes its contribution to the DAP. I(NaP) is thus neither sufficient nor necessary to generate the calyx DAP, whereas I(NaR) by itself can generate a prominent DAP. Dialysis of a small peptide fragment of the auxiliary β4 Na(+) channel subunit into immature calyces (postnatal day 5-6) induced an increase in I(NaR) and a larger DAP amplitude, and enhanced the spike-firing precision and reliability of the calyx terminal. Our results thus suggest that an increase of I(NaR) during postnatal synaptic maturation is a critical feature that promotes precise and resilient high-frequency firing.
authors.affiliation: The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Christopher
authors.initials: C
authors.lastname: Kushmerick
authors.forename: Henrique
authors.initials: H
authors.lastname: von Gersdorff
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000502:physiology*; D002490:Central Nervous System / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015222:Sodium Channels