Isoflurane hyperpolarizes neurones in rat and human cerebral cortex

Area of Science:

• Neuroscience
• Anesthesiology
• Cellular Electrophysiology

Background:

• Isoflurane is a widely used inhalation anesthetic.
• Understanding its precise cellular mechanisms is crucial for safe anesthetic practice.

Purpose of the Study:

• To investigate the direct effects of isoflurane on neuronal membrane potential and excitability.
• To compare the effects of isoflurane on rat hippocampal and human neocortical neurons.

Main Methods:

• Intracellular recordings were performed on isolated rat hippocampal and human neocortical neurons in vitro.
• Neurons were exposed to varying concentrations of isoflurane (1.5%, 3%, 5%).
• Effects on spontaneous and evoked synaptic activity, membrane potential, and input resistance were measured.

Main Results:

• Isoflurane abolished spontaneous neuronal activity and reduced evoked synaptic activity in a dose-dependent manner.
• Neurons remained excitable and capable of responding to increased afferent input.
• Isoflurane induced a reversible hyperpolarization of the cell membrane (4-8 mV) and decreased input resistance (18% at 3% isoflurane).
• These effects were observed in both rat and human neurons and persisted even after blocking synaptic transmission.

Conclusions:

• Isoflurane exerts direct electrophysiological effects on cortical neurons, primarily through hyperpolarization and reduced input resistance.
• These cellular actions contribute to the anesthetic properties of isoflurane without causing neuronal inexcitability.
• The findings in rat models are consistent with effects observed in human cortical neurons, supporting isoflurane's safety profile.