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Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G Meuth, Florian Lesage
Recombinant TWIK2 channels produce weak basal background K+ currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308 ASIP) and di-leucine-like (E266 LILL and D282 EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane...
April 5, 2017: Scientific Reports
Delphine Bichet, Sandy Blin, Sylvain Feliciangeli, Franck C Chatelain, Nicole Bobak, Florian Lesage
Among K2P channels, a few of them turned out to be difficult to express in heterologous systems and were coined "silent subunits". Recent studies have shed light on the mechanisms behind this apparent lack of channel activity at the plasma membrane. For TWIK1 and THIK2 channels, silence is related to a combination of intracellular retention and low intrinsic activity. TWIK1 is constitutively endocytosed from the plasma membrane before being transported to recycling endosomes, whereas THIK2 is restricted to endoplasmic reticulum...
May 2015: Pflügers Archiv: European Journal of Physiology
Barnaby Marsh, Cristian Acosta, Laiche Djouhri, Sally N Lawson
Two pore domain potassium (K2P) channels (KCNKx.x) cause K⁺ leak currents and are major contributors to resting membrane potential. Their roles in dorsal root ganglion (DRG) neurons normally, and in pathological pain models, are poorly understood. Therefore, we examined mRNA levels for 10 K2P channels in L4 and L5 rat DRGs normally, and 1 day and 4 days after unilateral cutaneous inflammation, induced by intradermal complete Freund's adjuvant (CFA) injections. Spontaneous foot lifting (SFL) duration (spontaneous pain behaviour) was measured in 1 day and 4 day rats <1h before DRG harvest...
March 2012: Molecular and Cellular Neurosciences
Kyoung Sun Park, Bo Pang, Su Jung Park, Yun-Gyoo Lee, Ji-Yeon Bae, Seonyang Park, Inho Kim, Sung Joon Kim
Hematopoietic stem cells (HSCs) are used therapeutically for hematological diseases and may also serve as a source for nonhematopoietic tissue engineering in the future. In other cell types, ion channels have been investigated as potential targets for the regulation of proliferation and differentiation. However, the ion channels of HSCs remain elusive. Here, we functionally characterized the ion channels of CD34(+) cells from human peripheral blood. Using fluorescence-activated cell sorting, we confirmed that the CD34(+) cells also express CD45 and CD133...
August 2011: Molecules and Cells
Joseph Yanni, James O Tellez, Michal Maczewski, Urszula Mackiewicz, Andrzej Beresewicz, Rudi Billeter, Halina Dobrzynski, M R Boyett
BACKGROUND: Heart failure (HF) causes a decline in the function of the pacemaker of the heart-the sinoatrial node (SAN). The aim of the study was to investigate HF-induced changes in the expression of the ion channels and related proteins underlying the pacemaker activity of the SAN. METHODS AND RESULTS: HF was induced in rats by the ligation of the proximal left coronary artery. HF animals showed an increase in the left ventricular (LV) diastolic pressure (317%) and a decrease in the LV systolic pressure (19%) compared with sham-operated animals...
July 2011: Circulation. Heart Failure
Huan Zhao, Leslie K Sprunger, Steven M Simasko
Vagal afferent neurons relay important information regarding the control of the gastrointestinal system. However, the ionic mechanisms that underlie vagal activation induced by sensory inputs are not completely understood. We postulate that transient receptor potential (TRP) channels and/or two-pore potassium (K2p) channels are targets for activating vagal afferents. In this study we explored the distribution of these channels in vagal afferents by quantitative PCR after a capsaicin treatment to eliminate capsaicin-sensitive neurons, and by single-cell PCR measurements in vagal afferent neurons cultured after retrograde labeling from the stomach or duodenum...
February 2010: American Journal of Physiology. Gastrointestinal and Liver Physiology
Christina C Young, Michael Stegen, René Bernard, Martin Müller, Josef Bischofberger, Rüdiger W Veh, Carola A Haas, Jakob Wolfart
In humans, temporal lobe epilepsy (TLE) is often associated with Ammon's horn sclerosis (AHS) characterized by hippocampal cell death, gliosis and granule cell dispersion (GCD) in the dentate gyrus. Granule cells surviving TLE have been proposed to be hyperexcitable and to play an important role in seizure generation. However, it is unclear whether this applies to conditions of AHS. We studied granule cells using the intrahippocampal kainate injection mouse model of TLE, brain slice patch-clamp recordings, morphological reconstructions and immunocytochemistry...
September 1, 2009: Journal of Physiology
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