The metabolic cost of action potential (AP) generation is largely determined by the ATP required for restoring the ionic gradients associated with Na⁺ influx and K⁺ efflux via voltage-gated ion channels. Recently, AP conduction in hippocampal mossy fiber boutons was found to be surprisingly efficient; during the downstroke of the AP (half-duration ~250 µs) the Na⁺ influx is rapidly inactivated and precisely timed with the onset of K⁺ efflux [1]. However, APs of similar half-duration in the axon initial segment of layer 5 pyramidal neurons have lower metabolic efficiency, which facilitates high-frequency AP initiation [2]. Furthermore, recordings from somata of different cell types indicate that cells with short AP durations have metabolically less efficient APs [3, 4]. To analyze the metabolic costs of high-frequency APs, we established direct whole-cell patch-clamp recordings from cerebellar mossy fiber boutons, which can fire in the kHz range. The AP half-duration was exceptionally short (129 ± 3 µs, n = 110, 35 °C). The AP evoked inward current measured in outside-out patches from cerebellar mossy fiber boutons had a half-duration of 70 ± 7 µs (n = 6), and 159 ± 11 µs (n = 2) when the Na⁺ current was pharmacologically isolated. The Na⁺ excess ratio (determined as ratio of total Na⁺ flux vs. Na⁺ flux until the time of AP peak) was 4 ± 0.4 (n = 2). These data suggest that metabolic inefficiency with substantial excess Na+ influx underlie high-frequency APs in cerebellar mossy fiber boutons.

1 Alle H et al. (2009) Science 325: 1405-1408

2 Hallermann S et al. (2012) Nat. Neurosci. 15: 1007-1014

3 Carter BC and Bean BP (2009) Neuron 64: 898-909

4 Carter BC and Bean BP (2011) J. Neurophysiol. 105: 860-871