Activation of TREK currents by the neuroprotective agent riluzole in mouse sympathetic neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Ion Channel Physiology

Background:

• K2P channels are vital for regulating resting membrane potential and neuronal excitability in the central and peripheral nervous systems.
• Mouse superior cervical ganglion (mSCG) neurons were investigated for K2P channel expression and function.

Purpose of the Study:

• To investigate the presence and function of K2P channels in the mammalian autonomic nervous system.
• To characterize the properties of a novel riluzole-activated potassium current (I(RIL)) in mSCG neurons.

Main Methods:

• Whole-cell electrophysiology was used to record and analyze the riluzole-activated current (I(RIL)).
• Reverse transcription-PCR and immunocytochemistry were employed to detect TREK-1, TREK-2, and TRAAK mRNA and protein expression.
• Cell-attached patch-clamp recordings were performed to confirm channel identity.

Main Results:

• A potassium-transporting current (I(RIL)) activated by riluzole, linoleic acid, membrane stretch, and internal acidification was identified in mSCG neurons.
• TREK-1, TREK-2, and TRAAK mRNA and protein were expressed in mSCG neurons.
• I(RIL) exhibited properties consistent with TREK-1/2 channels, including rectification and sensitivity to specific modulators like zinc, barium, and fluoxetine.
• Patch-clamp recordings confirmed the presence of TREK-2 channels in most mSCG neurons.

Conclusions:

• This study provides the first evidence of K2P channel expression in the mammalian autonomic nervous system.
• TREK-1 and TREK-2 channels are functionally expressed in mSCG neurons and contribute to neuronal excitability.
• The findings expand the known roles of K2P channels across the entire nervous system.