Two-pore domain potassium channels (2PK) make up the newest branch of the potassium channel super-family. The channels are time- and voltage-independent and carry leak or "background" currents that are regulated by many different signaling molecules. These currents play an important role in setting the resting membrane potential and excitability of excitable cells, and, as a consequence, modulation of 2PK channel activity is thought to underlie the function of physiological processes as diverse as the sedation of anesthesia, regulation of normal cardiac rhythm and synaptic plasticity associated with simple forms of learning. Lipids, including arachidonate and its lipoxygenase metabolites, platelet-activating factor and anandamide have been identified as important mediators of some 2PK channels. Regulation can be effected by several different mechanisms. Some channels are regulated by G-protein-coupled receptors using well described signaling pathways that terminate in the activation of protein kinase C, whereas others are modulated by the direct interaction of the lipid with the channel.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.prostaglandins.2004.10.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sea Anemone Kunitz Peptide HCIQ2c1: Structure, Modulation of TRPA1 Channel, and Suppression of Nociceptive Reaction In Vivo.
Mar Drugs
December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 119997 Moscow, Russia.
TRPA1 is a homotetrameric non-selective calcium-permeable channel. It contributes to chemical and temperature sensitivity, acute pain sensation, and development of inflammation. HCIQ2c1 is a peptide from the sea anemone that inhibits serine proteases.
View Article and Find Full Text PDFThe molecular basis of pH sensing by the human fungal pathogen TOK potassium channel.
iScience
December 2024
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.
View Article and Find Full Text PDFIn the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retina's ability to encode diverse visual features.
View Article and Find Full Text PDFCannabinoid inhibition of mechanosensitive K channels.
bioRxiv
December 2024
Department of Molecular & Cell Biology, Department of Neuroscience, California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, California 94720, USA.
Cannabidiol (CBD) is a prominent non-psychoactive small molecule produced by cannabis plants used clinically as an antiepileptic. Here, we show CBD and other cannabinoids are potent inhibitors of mechanosensitive two-pore domain K (K2P) channels, including TRAAK and TREK-1 that contribute to spike propagation in myelinated axons. Five TRAAK mutations that cause epilepsy or the neurodevelopmental syndrome FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth) retain sensitivity to cannabinoid inhibition.
View Article and Find Full Text PDF3D Aligned Tetrameric Ion Channels with Universal Residue Labels for Comparative Structural Analysis.
Biophys J
December 2024
I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, St. Petersburg, Russia; Department of Biochemistry and Biomedical Sciences, Master University, Hamilton, Canada. Electronic address:
Despite their large functional diversity and poor sequence similarity, tetrameric and pseudo-tetrameric potassium, sodium, calcium and cyclic-nucleotide gated channels, as well as two-pore channels, transient receptor potential channels and ionotropic glutamate receptors share a common folding pattern of the transmembrane (TM) helices in the pore-forming domain. In each subunit or repeat, the pore domain has two TM helices connected by a membrane-reentering P-loop. The P-loop includes a membrane-descending helix, P1, which is structurally the most conserved element of these channels, and residues that contribute to the selectivity-filter region at the constriction of the ion-permeating pathway.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!