Expression of K2P Channels in Sensory and Motor Neurons of the Autonomic Nervous System

Abstract

Several types of neurons within the central and peripheral somatic nervous system express two-pore-domain potassium (K2P) channels, providing them with resting potassium conductances. We demonstrate that these channels are also expressed in the autonomic nervous system where they might be important modulators of neuronal excitability. We observed strong mRNA expression of members of the TRESK and TREK subfamilies in both the mouse superior cervical ganglion (mSCG) and the mouse nodose ganglion (mNG). Motor mSCG neurons strongly expressed mRNA transcripts for TRESK and TREK-2 subunits, whereas TASK-1 and TASK-2 subunits were only moderately expressed, with only few or very few transcripts for TREK-1 and TRAAK (TRESK ≈ TREK-2 > TASK-2 ≈ TASK-1 > TREK-1 > TRAAK). Similarly, the TRESK and TREK-1 subunits were the most strongly expressed in sensorial mNG neurons, while TASK-1 and TASK-2 mRNAs were moderately expressed, and fewer TREK-2 and TRAAK transcripts were detected (TRESK ≈ TREK-1 > TASK-1 ≈ TASK-2 > TREK-2 > TRAAK). Moreover, cell-attached single-channel recordings showed a major contribution of TRESK and TREK-1 channels in mNG. As the level of TRESK mRNA expression was not statistically different between the ganglia analysed, the distinct expression of TREK-1 and TREK-2 subunits was the main difference observed between these structures. Our results strongly suggest that TRESK and TREK channels are important modulators of the sensorial and motor information flowing through the autonomic nervous system, probably exerting a strong influence on vagal reflexes.

Formation of Functional Heterodimers by TREK-1 and TREK-2 Two-pore Domain Potassium Channel Subunits

“…Native channels with properties corresponding to TREK-1 and TREK-2 and a TREKlike channel (with properties different from TREK-1, TREK-2, and TRAAK) have been described in magnocellular neurosecretory cells of the supraoptic nucleus (36). The expression of both subunits has also been detected in the peripheral (27)(28)(29) superior cervical ganglia (37). Coexpression of TREK-1 and TREK-2 subunits has also been described in non-neuronal cells, for example in pulmonary vascular smooth muscle cells (31).…”

KCNK18 (TRESK) Genetic Variants in Italian Patients With Migraine

“…TRESK is abundantly expressed in the trigeminal ganglion and dorsal root ganglia, 10,11,20 suggesting that this channel may play a key role in neurons crucial to migraine pathogenesis. 22,23 In addition, due to the coupling of TRESK to the histamine H1 receptor, the channel may reduce neuronal excitability in inflammatory conditions, like during the migraine attack when inflammatory modulators are released into the surrounding tissues. 21 TRESK is also expressed in human autonomic nervous system ganglia that may be chronically altered in migraine.…”

“…21 TRESK is also expressed in human autonomic nervous system ganglia that may be chronically altered in migraine. 22,23 In addition, due to the coupling of TRESK to the histamine H1 receptor, the channel may reduce neuronal excitability in inflammatory conditions, like during the migraine attack when inflammatory modulators are released into the surrounding tissues. 24,25 Finally, it is of interest to notice that, outside the nervous system, TRESK is abundantly expressed in several organs of the immune system, like the thymus, the spleen, and T lymphocytes, suggesting a role for this channel for neuroimmune interactions.…”

Tubulin Binds to the Cytoplasmic Loop of TRESK Background K+ Channel In Vitro

“…Later, general consensus was reached that TRESK is robustly expressed in pseudounipolar neurons of dorsal root, trigeminal and other sensory ganglia [13]–[19]. At present, these ganglia are considered as the major location of the channel, although some evidence is accumulating that it may also be important in ganglia of the autonomic nervous system [20], and in lymphoblastic cell lines [21], [22].…”