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Lactate activates KCNK2. 18 / 18
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"Using patch clamp electrophysiology on acute brain slices and heterologously expressed human (h) TREK1 in cells of the human embryonic kidney 293 cell line (HEK293) we observed that lactate increases TREK1 current."
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"NeuroscienceThe Journal of PhysiologyJ Physiol 594.1 (2016) pp 59-8159Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domainSwagata Ghatak, Aditi Banerjee and Sujit Kumar SikdarMolecular Biophysics Unit, Indian Institute of Science, Bangalore, Karnataka 560012, IndiaKey pointsr The physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1are known neuroprotectants against cerebral ischaemia."
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"Similarly, when 30 mM lactate was applied with 100 muM fluoxetine, another TREK1 channel blocker, lactate was unable to increase whole cell TREK1 currents in CA1sr astrocytes."
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"Basal concentrations of lactate do not increase TREK1 channel activity in CA1sr astrocytes in hippocampal slicesC 2015 The Authors."
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"The findings of our study have important implications since ischaemic concentrations of lactate increase TREK1 activity which might promote efficient potassium clearance, spatial buffering and volume regulation.Current therapeutic interventions used for the early treatment of ischaemic stroke involve administration of tissue plasminogen activator (tPA, thrombolytic therapy), aspirin, dipyridamole and clopidogrel (antiplatelet therapy), and heparin, warfarin and dabigatran (anticoagulant therapy) (Mocco et al. 2007; Whitehead et al. 2007; Melani et al. 2010; Woodruff et al. 2011; Kono et al. 2014; Ozdemir et al. 2014)."
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"Application of 30 mM lactate along with non specific MCT blocker 2 mM alpha-cyano-4-hydroxycinnamate (4CIN) did not increase TREK1 current beyond control levels (Figs 1E and 3A)."
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"Ischaemic concentrations of lactate increased whole cell TREK1 current of rat CA1sr astrocytes."
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"30 mM lactate increased TREK1 current by 17.4 +/- 3.7% at 20 mV compared to 2.3 +/- 2% at -160 mV, indicating a preferential increase in conductance at depolarized potentials."
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"The physiological relevance of our experiments is supported by the observation that TREK1 channels are activated by ischaemic concentrations but not by basal concentrations of lactate."
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"We subtracted the lactate induced whole cell TREK1 current traces from their respective control current traces to reveal its outward rectifying profile."
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"In our earlier studies we showed that high levels of lactate can increase TREK1 channel activity and expression within 1 "
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"In this study we show that lactate increases TREK1 channel activityandhyperpolarizesCA1rstratum radiatum astrocytes in hippocampal slices."
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"During ischemia, the ischemic metabolite lactate elevates TREK-1 in astrocytes via the protein kinase A pathway (Banerjee et al., 2016)."
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"Pyruvate failed to activate TREK1 current, clearly indicating that lactate specifically increases the activity of TREK1 channels in CA1sr astrocytes."
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"In the present study, we show that ischaemic concentrations of lactate (30mM) at pH 7.0 and 6.5, commonly observed during ischemia, cause robust potentiation of human TREK1 (hTREK1) activity at single-channel level in cell-free inside-out membrane patches, while 30mM lactate at pH 6.0 to 5.5, commonly observed during hyperglycaemic ischemia, reduces hTREK1 channel activity significantly."
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"During ischemia, the ischemic metabolite lactate upregulates TREK-1 in astrocytes via the PKA pathway [113]."
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"Note the outward rectification of the whole cell lactate induced TREK1 currents in the subtracted traces in B and C. Note the profiles of subtracted traces in A and D which indicate no change of whole cell TREK1 current with basal concentrations of lactate and 30 mM pyruvate."
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"Prolonged exposure to lactate causes TREK1 channel clustering in rat hippocampal astrocytes."
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