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Journal ArticleDOI

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium.

30 Oct 2021-Biology (Multidisciplinary Digital Publishing Institute)-Vol. 10, Iss: 11, pp 1119
TL;DR: In this article, the PI(4,5)P2-dependent mechanism of channel activity was investigated in rat prefrontal cortex and it was shown that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics.
Abstract: TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity—from very low to very high—independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity. Single-channel patch clamp recordings were performed on freshly dissociated pyramidal neurons of rat prefrontal cortexes in both the cell-attached and inside-out configurations. To evaluate the role of endogenous stimulants, the activity of the channels was recorded in the presence of a PI(4,5)P2 analogue (PI(4,5)P2DiC8) and Ca2+. Our research revealed that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics. The observation that calcium participates in the activation of TREK-2-like channels is a new finding. We showed that PI(4,5)P2-dependent TREK-2 activity occurs when the conditions for PI(4,5)P2/Ca2+ nanocluster formation are met. We present a possible model explaining the mechanism of calcium action.
References
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Journal ArticleDOI
TL;DR: Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis that facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system.
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43,540 citations

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TL;DR: This review focuses on the physiological roles of K(2P) channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.
Abstract: Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and c...

734 citations

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TL;DR: This paper argues for the validity of a representational approach to understanding PFC function and suggests that the prefrontal cortex underlies much of human higher cognition.
Abstract: Through evolution, humans have acquired 'higher' cognitive skills — such as language, reasoning and planning — and complex social behaviour. Evidence from neuropsychological and neuroimaging research indicates that the prefrontal cortex (PFC) underlies much of this higher cognition. A number of theories have been proposed for how the PFC might achieve this. Although many of these theories focus on the types of 'process' that the PFC carries out, we argue for the validity of a representational approach to understanding PFC function.

667 citations

Journal ArticleDOI
TL;DR: The discovery of KCNK channels is reviewed, what has been learned about them and what lies ahead: highly regulated, potassium-selective leak channels that function in a most remarkable fashion.
Abstract: With a bang, a new family of potassium channels has exploded into view. Although KCNK channels were discovered only five years ago, they already outnumber other channel types. KCNK channels are easy to identify because of their unique structure--they possess two preforming domains in each subunit. The new channels function in a most remarkable fashion: they are highly regulated, potassium-selective leak channels. Although leak currents are fundamental to the function of nerves and muscles, the molecular basis for this type of conductance had been a mystery. Here we review the discovery of KCNK channels, what has been learned about them and what lies ahead. Even though two-P-domain channels are widespread and essential, they were hidden from sight in plain view--our most basic questions remain to be answered.

659 citations

Journal ArticleDOI
TL;DR: TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system and has been suggested to be an important target in the action of these drugs as discussed by the authors.
Abstract: TREK-1 is a two-pore-domain background potassium channel expressed throughout the central nervous system. It is opened by polyunsaturated fatty acids and lysophospholipids. It is inhibited by neurotransmitters that produce an increase in intracellular cAMP and by those that activate the Gq protein pathway. TREK-1 is also activated by volatile anesthetics and has been suggested to be an important target in the action of these drugs. Using mice with a disrupted TREK-1 gene, we now show that TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal chord ischemia. Trek1−/− mice display an increased sensitivity to ischemia and epilepsy. Neuroprotection by polyunsaturated fatty acids, which is impressive in Trek1+/+ mice, disappears in Trek1−/− mice indicating a central role of TREK-1 in this process. Trek1−/− mice are also resistant to anesthesia by volatile anesthetics. TREK-1 emerges as a potential innovative target for developing new therapeutic agents for neurology and anesthesiology.

482 citations

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