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.
Highlights
Mammalian two-pore-domain potassium (K2P) channels, discovered in 1996 [1], have been shown to be expressed in many neuronal types of the central and peripheral somatic nervous system [2,3,4]
Cells unresponsive to capsaicin and without TTX resistant sodium currents were classified as A-type, those unresponsive to capsaicin and showing both TTX-sensitive and resistant (TTX-SR) sodium currents were Ah-type, and cells responding to capsaicin and having TTX-SR currents were defined as C-type. Using this newly developed classification of isolated mouse nodose ganglion (mNG) neurons, we report here that all types of nodose ganglion neurons respond to riluzole and other TREK modulators, suggesting that they express one or more types of TREK subfamily channels (TREK-1, TREK-2 and TRAAK)
Capacitance differences between A and C type cells were previously reported in NG neurons from rabbit [18], and two populations with different soma size have been reported in rat dorsal root ganglia (DRG) neurons [10]
Summary
Mammalian two-pore-domain potassium (K2P) channels, discovered in 1996 [1], have been shown to be expressed in many neuronal types of the central and peripheral somatic nervous system [2,3,4]. Only a small group of pioneering studies have reported that K2P channels are expressed in neurons of the rat and mouse autonomic nervous system [5,6,7]. TREK currents in subpopulations of mouse nodose neurons (GPC2015/022) and European Regional Development Fund (FP7-316265-BIOCAPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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