TY - JOUR
T1 - Presynaptic resurgent Na+ currents sculpt the action potential waveform and increase firing reliability at a CNS nerve terminal
AU - Kim, Jun Hee
AU - Kushmerick, Christopher
AU - Von Gersdorff, Henrique
PY - 2010/11/17
Y1 - 2010/11/17
N2 - 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 (INaR), the amplitude of which increased during early postnatal development. The calyx of Held also expresses a persistent Na+ current (INaP), but measurements of calyx INaP together with computer modeling indicate that the fast deactivation time constant of INaP minimizes its contribution to the DAP. INaP is thus neither sufficient nor necessary to generate the calyx DAP, whereas INaR 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 INaR 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 INaR during postnatal synaptic maturation is a critical feature that promotes precise and resilient high-frequency firing.
AB - 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 (INaR), the amplitude of which increased during early postnatal development. The calyx of Held also expresses a persistent Na+ current (INaP), but measurements of calyx INaP together with computer modeling indicate that the fast deactivation time constant of INaP minimizes its contribution to the DAP. INaP is thus neither sufficient nor necessary to generate the calyx DAP, whereas INaR 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 INaR 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 INaR during postnatal synaptic maturation is a critical feature that promotes precise and resilient high-frequency firing.
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U2 - 10.1523/JNEUROSCI.3982-10.2010
DO - 10.1523/JNEUROSCI.3982-10.2010
M3 - Article
C2 - 21084604
AN - SCOPUS:78449246774
SN - 0270-6474
VL - 30
SP - 15479
EP - 15490
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -