In myelinated nerve fibres, action potentials are generated at nodes of Ranvier. These structures are located at interruptions of the myelin sheath, forming narrow gaps with small rings of axolemma freely exposed to the extracellular space. The mammalian node contains a high density of Na channels and K -selective leakage channels. Voltage-dependent Kv1 channels are only present in the juxta-paranode. Recently, the leakage channels have been identified as K2P channels (TRAAK, TREK-1). K2P channels are K -selective 'background' channels, characterized by outward rectification and their ability to be activated, e.g. by temperature, mechanical stretch or arachidonic acid. We are only beginning to elucidate the peculiar functions of nodal K2P channels. I will discuss two functions of the nodal K2P-mediated conductance. First, at body temperature K2P channels have a high open probability, thereby inducing a resting potential of about -85 mV. This negative resting potential reduces steady-state Na channel inactivation and ensures a large Na inward current upon a depolarizing stimulus. Second, the K2P conductance is involved in nodal action potential repolarization. The identification of nodal K2P channels is exciting since it shows that the nodal K conductance is not a fixed value but can be changed: it can be increased or decreased by a broad range of K2P modulators, thereby modulating, for example, the resting potential. The functional importance of nodal K2P channels will be exemplified by describing in more detail the function of the K2P conductance increase by raising the temperature from room temperature to 37°C.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1113/JP281723 | DOI Listing |
Biochem Biophys Res Commun
January 2025
Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea. Electronic address:
Schizophrenia (SCZ) and bipolar disorder (BD) and are severe psychiatric conditions that contribute to disability and increased healthcare costs globally. Although first-, second-, and third-generation antipsychotics are available for treating BD and SCZ, most have various side effects unrelated to their unique functions. Many antipsychotics affect K channels (Kv, K, Kir, K, and other channels), which change the functions of various organs.
View Article and Find Full Text PDFiScience
January 2025
School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.
TWIK-1 belongs to the two-pore domain K (K2P) channel family, which plays an essential role in the background K conductance of cells. Despite the development of exon 2-deleted knockout (KO) mice, the physiological role of TWIK-1 has remained largely unknown. Here, we observed that the exon 2-deleted KO mice expressed an internally deleted TWIK-1 (TWIK-1 ΔEx2) protein, which unexpectedly acts as a functional K channel.
View Article and Find Full Text PDFEur J Orthod
December 2024
Division of Paediatric Dentistry & Orthodontics, Faculty of Dentistry, the University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, China.
Background: Periodontal ligament cells (PDLCs) possess mechanotransduction capability, vital in orthodontic tooth movement (OTM) and maintaining periodontal homeostasis. The study aims to elucidate the expression profiles of mechanosensitive ion channel (MIC) families in PDLCs and how the inflammatory mediator alters their expression and function, advancing the understanding of the biological process of OTM.
Methods And Methods: Human PDLCs were cultured and exposed to TNF-α.
Sheng Li Xue Bao
December 2024
School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Two-pore-domain potassium channels (K2P) family is widely expressed in many human cell types and organs, which has important regulatory effect on physiological processes. K2P is sensitive to a variety of chemical and physical stimuli, and they have also been critically implicated in transmission of neural signal, ion homeostasis, cell development and death, and synaptic plasticity. Aberrant expression and dysfunction of K2P channels are involved in a range of diseases, including autoimmune, central nervous system, cardiovascular disease and others.
View Article and Find Full Text PDFbioRxiv
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 PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!