Activation of TREK currents by riluzole in three subgroups of cultured mouse nodose ganglion neurons

Abstract

Two-pore domain potassium channels (K2P) constitute major candidates for the regulation of background potassium currents in mammalian cells. Channels of the TREK subfamily are also well positioned to play an important role in sensory transduction due to their sensitivity to a large number of physiological and physical stimuli (pH, mechanical, temperature). Following our previous report describing the molecular expression of different K2P channels in the vagal sensory system, here we confirm that TREK channels are functionally expressed in neurons from the mouse nodose ganglion (mNG). Neurons were subdivided into three groups (A, Ah and C) based on their response to tetrodotoxin and capsaicin. Application of the TREK subfamily activator riluzole to isolated mNG neurons evoked a concentration-dependent outward current in the majority of cells from all the three subtypes studied. Riluzole increased membrane conductance and hyperpolarized the membrane potential by approximately 10 mV when applied to resting neurons. The resting potential was similar in all three groups, but C cells were clearly less excitable and showed smaller hyperpolarization-activated currents at -100 mV and smaller sustained currents at -30 mV. Our results indicate that the TREK subfamily of K2P channels might play an important role in the maintenance of the resting membrane potential in sensory neurons of the autonomic nervous system, suggesting its participation in the modulation of vagal reflexes.

Early Stimulation of TREK Channel Transcription and Activity Induced by Oxaliplatin-Dependent Cytosolic Acidification

“…Because in these ionic conditions, the actual reversal potential (V rev ) is very difficult to evaluate, we performed a series of experiments replacing 130 mM CsCl with 150 mM KCl in the pipette solution. These conditions allowed us to observe the inward rectifying behavior that characterizes TREK-2 channels [ 25 , 28 ]. The traces in Figure 3 D represent examples of single-channel openings recorded in an OHP-treated neuron by applying a 500 ms voltage ramp from −120 mV to 50 mV, after baseline subtraction and plotted against the voltage.…”

Serotonergic Modulation of Persistent Inward Currents in Serotonergic Neurons of Medulla in ePet-EYFP Mice

“…Similar results are also observed in 5-HT neurons of dorsal raphe nucleus in juvenile mice, where PIC amplitude is about nine times the rheobase ( Ge and Dai, 2020 ). Therefore, we speculate that these differences may be due to different types of neurons and functional roles in regulating neuronal excitabilities for different behaviors such as mental ( Meera et al, 2003 ; Kang et al, 2019 ) or physiological behaviors ( Fernandez-Fernandez et al, 2018 ; Hsu et al, 2018 ).…”

Contribution of Neuronal and Glial Two-Pore-Domain Potassium Channels in Health and Neurological Disorders

“…Activating TREKs using the neuroprotective agent riluzole hyperpolarized the resting membrane in the superior cervical ganglion [35,36]. Similarly, activating TREK-1/2 in DRG neurons with BL-1249 or GI-530159 hyperpolarized the resting membrane and reduced firing frequency [37].…”