Extracellular divalent ions modulate TREK-2-like channel conductance in prefrontal pyramidal neurons in rats
, 1, 2
Abstract
Background: The aim of the study was to investigate, with the use of the patch clamp technique, the dependence of the conductance of the TREK-2-like potassium leak channel in the medial prefrontal cortex
pyramidal neurons on the presence of extracellular magnesium and calcium ions. It is suspected that
TREK-2 channels regulate mood and may be associated with the pathophysiology of depression. Since
magnesium and calcium deficiency contribute to depressive symptoms, we investigated how TREK-2- like
channel pore propertie change in the absence of divalent cations.
Results: Single-channel currents were recorded in a cell-attached configuration in enzymatically dispersed
pyramidal neurons of the prefrontal cortex in rats. Spontaneous TREK-2-like channel activity was recorded
either in the presence or absence of magnesium and calcium ions in extracellular solution. A significant
increase in the inward channel conductance was observed when divalent cations were removed from
the extracellular solution. Inward rectification was also increased when the bath temperature was raised
to 34-37°C.
Conclusions: The study confirmed that the activity of TREK-2-like channels is affected by the presence of
magnesium and calcium ions in the extracellular solution. Therefore, in vivo, the TREK-2-like channel may
possibly participate in the prefrontal cortex dysfunction associated with the deficiency of divalent cations.
Keywords: magnesium and calcium homeostasisdepressionTREK-2 channelsleak potassium channelspatch-clamp
References
- Kokot F. Zaburzenia Gospodarki Wodno-Elektrolitowej i Kwasowo-Zasadowej. Second edi. Wydawnictwo Lekarskie PZWL .
- Serefko A, Szopa A, Wlaź P, et al. Magnesium in depression. Pharmacol Reports. 2013; 65(3): 547–554.
- Ordak M, Matras J, Muszynska E, et al. Magnesium in schizophrenia. Pharmacol Rep. 2017; 69(5): 929–934.
- Deutschenbaur L, Beck J, Kiyhankhadiv A, et al. Role of calcium, glutamate and NMDA in major depression and therapeutic application. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 64: 325–333.
- Młyniec K, Davies CL, de Agüero Sánchez IG, et al. Essential elements in depression and anxiety. Part I. Pharmacol Rep. 2014; 66(4): 534–544.
- Ładno W, Gawlak M, Szulczyk P, et al. Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons. Brain Res. 2017; 1665: 95–104.
- Gu W, Schlichthörl G, Hirsch JR, et al. Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. J Physiol. 2002; 539(Pt 3): 657–668.
- Kim EJ, Lee DK, Hong SG, et al. Activation of TREK-1, but Not TREK-2, Channel by Mood Stabilizers. Int J Mol Sci. 2017; 18(11).
- Heurteaux C, Lucas G, Guy N, et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci. 2006; 9(9): 1134–1141.
- Park H, Kim EJ, Han J, et al. Effects of analgesics and antidepressants on TREK-2 and TRESK currents. Korean J Physiol Pharmacol. 2016; 20(4): 379–385.
- Guo D, Ramu Y, Klem AM, et al. Mechanism of rectification in inward-rectifier K+ channels. J Gen Physiol. 2003; 121(4): 261–275.
- Yang L, Edvinsson J, Palmer LG. Interactions of external K+ and internal blockers in a weak inward-rectifier K+ channel. J Gen Physiol. 2012; 140(5): 529–540.
- Nguyen A, Wong A, Oberoi A, et al. The cardiac potassium channel HERG is blocked by calcium at a site near the outer mouth of the channel. FASEB J. 2015; 29(No. 1 supplement; abstract No. 553.6).
- Lesage F, Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol. 2000; 279(5): F793–F801.
- Kennard LE, Chumbley JR, Ranatunga KM, et al. Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. Br J Pharmacol. 2005; 144(6): 821–829.
- Moha ou Maati H, Peyronnet R, Devader C, et al. A human TREK-1/HEK cell line: a highly efficient screening tool for drug development in neurological diseases. PLoS One. 2011; 6(10): e25602.
- Kang D, Kim EJ, Han J. Direct Inhibitory Effect of Fluoxetine on TREK-2 Channel. Biophysical Journal. 2012; 102(3).