Alfaxalone does not have long‐term effects on goldfish pyramidal neuron action potential properties or GABAA receptor currents

TL;DR

This study shows that alfaxalone, an anesthetic, does not have lasting effects on goldfish brain neurons and can be used for same-day experiments.

Contribution

The study demonstrates that alfaxalone's effects on goldfish neurons are reversible within 3 hours, enabling same-day electrophysiological experiments.

Findings

Alfaxalone sedation did not significantly impact goldfish pyramidal neuron action potential properties.

A 3-hour washout period is required to reverse alfaxalone's effects on GABAA receptor currents in goldfish brain slices.

Abstract

Anesthetics have varying physiological effects, but most notably alter ion channel kinetics. Alfaxalone is a rapid induction and washout neuroactive anesthetic, which potentiates γ‐aminobutyric acid (GABA)‐activated GABAA receptor (GABAA‐R) currents. This study aims to identify any long‐term effects of alfaxalone sedation on pyramidal neuron action potential and GABAA‐R properties, to determine if its impact on neuronal function can be reversed in a sufficiently short timeframe to allow for same‐day electrophysiological studies in goldfish brain. The goldfish (Carassius auratus) is an anoxia‐tolerant vertebrate and is a useful model to study anoxia tolerance mechanisms. The results show that alfaxalone sedation did not significantly impact action potential properties. Additionally, the acute application of alfaxalone onto naive brain slices caused the potentiation of whole‐cell GABAA‐R current decay time and area under the curve. Following whole‐animal sedation with alfaxalone, a 3‐h wash of brain slices in alfaxalone‐free saline, with saline exchanged every 30 min, was required to remove any potentiating impact of alfaxalone on GABAA‐R whole‐cell currents. These results demonstrate that alfaxalone is an effective anesthetic for same‐day electrophysiological experiments with goldfish brain slices.

Alfaxalone is a rapid induction and washout neuroactive anesthetic, which potentiates γ‐aminobutyric acid (GABA)‐activated GABAA receptor currents. Our study determined that the effect of alfaxalone sedation on goldfish neuronal function is reversed after 3 h. These results demonstrate that alfaxalone is an effective anesthetic for same‐day electrophysiological experiments with goldfish brain slices.

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