Sodium leak channel, non-selective (NaVi) C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
The sodium leak channel, non selective (NC-IUPHAR tentatively recommends the nomenclature NaVi2.1, W.A. Catterall, personal communication) is structurally a member of the family of voltage-gated sodium channel family (Nav1.1-Nav1.9) [1,9]. In contrast to the latter, NaVi2.1, is voltage-insensitive (denoted in the subscript 'vi' in the tentative nomenclature) and possesses distinctive ion selectivity and pharmacological properties. NaVi2.1, which is insensitive to tetrodotoxin (10 µM), has been proposed to mediate the tetrodotoxin-resistant and voltage-insensitive Na+ leak current (IL-Na) observed in many types of neurone [2]. However, whether NaVi2.1 is constitutively active has been challenged [7]. NaVi2.1 is widely distributed within the central nervous system and is also expressed in the heart and pancreas specifically, in rodents, within the islets of Langerhans [1-2]. Recently, NaVi2.1 has been proposed to be a core effector for the action of inhibitory G proteins [5].
Channels and Subunits
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Navi2.1 C Show summary » |
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Further reading
How to cite this family page
Database page citation:
Sodium leak channel, non-selective (NaVi). Accessed on 14/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=126.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.
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In native and recombinant expression systems NaVi2.1 can be activated by stimulation of NK1 (in hippocampal neurones), neurotensin (in ventral tegmental area neurones) and M3 muscarinic acetylcholine receptors (in MIN6 pancreatic β-cells) and in a manner that is independent of signalling through G proteins [3,7]. Pharmacological and molecular biological evidence indicates such modulation to occur though a pathway that involves the activation of Src family tyrosine kinases. It is suggested that NaVi2.1 exists as a macromolecular complex with M3 receptors [7] and peptide receptors [3], in the latter instance in association with the protein UNC-80, which recruits Src to the channel complex [3,8]. By contrast, stimulation of Navi2.1 by decreased extracellular Ca2+ concentration is G protein dependent and involves a Ca2+-sensing G protein-coupled receptor and UNC80 which links Navi2.1 to the protein UNC79 in the same complex [4]. Navi2.1 null mutant mice have severe disturbances in respiratory rhythm and die within 24 hours of birth [2]. Navi2.1 heterozygous knockout mice display increased serum sodium concentrations in comparison to wildtype littermates and a role for the channel in osmoregulation has been postulated [6].