Characterization of temperature-sensitive leak K+ currents and expression of TRAAK, TREK-1, and TREK2 channels in dorsal root ganglion neurons of rats

Abstract

Leak K+ currents are mediated by two-pore domain K+ (K2P) channels and are involved in controlling neuronal excitability. Of 15 members of K2P channels cloned so far, TRAAK, TREK-1, and TREK-2 are temperature sensitive. In the present study, we show that strong immunoreactivity of TRAAK, TREK-1 and TREK-2 channels was present mainly in small-sized dorsal root ganglion (DRG) neurons of rats. The percentages of neurons with strong immunoreactivity of TRAAK, TREK-1 and TREK-2 channels were 27, 23, and 20%, respectively. Patch-clamp recordings were performed to examine isolated leak K+ currents on acutely dissociated small-sized rat DRG neurons at room temperature of 22 °C, cool temperature of 14 °C and warm temperature of 30 °C. In majority of small-sized DRG neurons recorded (76%), large leak K+ currents were observed at 22 °C and were inhibited at 14 °C and potentiated at 30 °C, suggesting the presence of temperature-sensitive K2P channels in these neurons. In a small population (18%) of small-sized DRG neurons, cool temperature of 14 °C evoked a conductance which was consistent with TRPM8 channel activation in cold-sensing DRG neurons. In these DRG neurons, leak K+ currents were very small at 22 °C and were not potentiated at 30 °C, suggesting that few temperature-sensitive K2P channels was present in cold-sensing DRG neurons. For DRG neurons with temperature-sensitive leak K+ currents, riluzole, norfluoxetine and prostaglandin F2α (PGE2α) inhibited the leak K+ currents at both 30 °C and 22 °C degree, and did not have inhibitory effects at 14 °C. Collectively, the observed temperature-sensitive leak K+ currents are consistent with the expression of temperature-sensitive K2P channels in small-sized DRG neurons.

How Plants Sense and Respond to Stressful Environments

“…For example, heat perception in mammals is mediated by both the TRANSIENT RECEPTOR POTENTIAL (TRP) cationic channel family and the TWIK-RELATED POTASSIUM (TREK) channel family present in neurons. Increasing temperatures led to depolarization and increased action potential firing of corresponding neurons (Voets et al, 2004;Viatchenko-Karpinski et al, 2018). In Caenorhabditis elegans, high sodium levels result in an influx of Ca 21 and membrane depolarization mediated by TRANSMEMBRANE CHANNEL LIKE1 (TMC1;Chatzigeorgiou et al, 2013).…”

Chronic morphine regulates TRPM8 channels via MOR-PKCβ signaling

“…Previous studies described menthol as being promiscuous in its targets with the possibility of modulating the activity of other thermosensors (TRPA1, TRPV3, TRPC5, Nav1.9 and two pore potassium channels) [11,26,28,44]. Yet, menthol inhibits the activity of most of these channels at the concentrations used, including TRPA1 which was considered to be a noxious cold sensor [11,[26][27][28]44]. At the molecular level, we found that MOR activation by morphine leads to a PKCβ-induced reduction of TRPM8 desensitization likely via phosphorylation of the two Ser residues 1040 and 1041.…”

“…Nonetheless, no significant change in mRNA expression was found for either TRPM8 or other cold sensitive TREK-1 and TRAAK channels ( Fig. S1c), implying a functional rather than transcriptional regulation of these neurons [11,[26][27][28].…”

Regulation of TRPM8 channels by PKCβ mediates morphine-induced cold hypersensitivity.

“…Previous studies described menthol as being promiscuous in its targets with the possibility of modulating the activity of other thermosensors (TRPA1, TRPV3, TRPC5, Nav1.9 and two pore potassium channels) [11,26,28,44]. Yet, menthol inhibits the activity of most of these channels at the concentrations used, including TRPA1 which was considered to be a noxious cold sensor [11,[26][27][28]44]. At the molecular level, we found that MOR activation by morphine leads to a PKCβ-induced reduction of TRPM8 desensitization likely via phosphorylation of the two Ser residues 1040 and 1041.…”

“…Nonetheless, no significant change in mRNA expression was found for either TRPM8 or other cold sensitive TREK-1 and TRAAK channels ( Fig. S1c), implying a functional rather than transcriptional regulation of these neurons [11, [26][27][28].…”