Details

Autor(en) / Beteiligte

• Ohura, Shunsuke
• Kamiya, Haruyuki

Titel

Sodium Channel-Dependent and -Independent Mechanisms Underlying Axonal Afterdepolarization at Mouse Hippocampal Mossy Fibers

Ist Teil von

• eNeuro, 2018-07, Vol.5 (4), p.ENEURO.0254-18.2018

Ort / Verlag

United States: Society for Neuroscience

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Action potentials propagating along axons are often followed by prolonged afterdepolarization (ADP) lasting for several tens of milliseconds. Axonal ADP is thought to be an important factor in modulating the fidelity of spike propagation during repetitive firings. However, the mechanism as well as the functional significance of axonal ADP remain unclear, partly due to inaccessibility to small structures of axon for direct electrophysiological recordings. Here, we examined the ionic and electrical mechanisms underlying axonal ADP using whole-bouton recording from mossy fiber terminals in mice hippocampal slices. ADP following axonal action potentials was strongly enhanced by focal application of veratridine, an inhibitor of Na channel inactivation. In contrast, tetrodotoxin (TTX) partly suppressed ADP, suggesting that a Na channel-dependent component is involved in axonal ADP. The remaining TTX-resistant Na channel-independent component represents slow capacitive discharge reflecting the shape and electrical properties of the axonal membrane. We also addressed the functional impact of axonal ADP on presynaptic function. In paired-pulse stimuli, we found that axonal ADP minimally affected the peak height of subsequent action potentials, although the rising phase of action potentials was slightly slowed, possibly due to steady-state inactivation of Na channels by prolonged depolarization. Voltage clamp analysis of Ca current elicited by action potential waveform commands revealed that axonal ADP assists short-term facilitation of Ca entry into the presynaptic terminals. Taken together, these data show that axonal ADP maintains reliable firing during repetitive stimuli and plays important roles in the fine-tuning of short-term plasticity of transmitter release by modulating Ca entry into presynaptic terminals.