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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).
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) [1,8]. 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 . However, whether NaVi2.1 is constitutively active has been challenged . 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].
* Key recommended reading is highlighted with an asterisk
Gilon P, Rorsman P. (2009) NALCN: a regulated leak channel. EMBO Rep., 10 (9): 963-4. [PMID:19662077]
Swayne LA, Mezghrani A, Lory P, Nargeot J, Monteil A. (2010) The NALCN ion channel is a new actor in pancreatic β-cell physiology. Islets, 2 (1): 54-6. [PMID:21099296]
1. Lee JH, Cribbs LL, Perez-Reyes E. (1999) Cloning of a novel four repeat protein related to voltage-gated sodium and calcium channels. FEBS Lett., 445 (2-3): 231-6. [PMID:10094463]
2. Lu B, Su Y, Das S, Liu J, Xia J, Ren D. (2007) The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm. Cell, 129 (2): 371-83. [PMID:17448995]
3. Lu B, Su Y, Das S, Wang H, Wang Y, Liu J, Ren D. (2009) Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature, 457 (7230): 741-4. [PMID:19092807]
4. Lu B, Zhang Q, Wang H, Wang Y, Nakayama M, Ren D. (2010) Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex. Neuron, 68 (3): 488-99. [PMID:21040849]
5. Sinke AP, Caputo C, Tsaih SW, Yuan R, Ren D, Deen PM, Korstanje R. (2011) Genetic analysis of mouse strains with variable serum sodium concentrations identifies the Nalcn sodium channel as a novel player in osmoregulation. Physiol. Genomics, 43 (5): 265-70. [PMID:21177381]
6. Swayne LA, Mezghrani A, Varrault A, Chemin J, Bertrand G, Dalle S, Bourinet E, Lory P, Miller RJ, Nargeot J et al.. (2009) The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line. EMBO Rep., 10 (8): 873-80. [PMID:19575010]
7. Wang H, Ren D. (2009) UNC80 functions as a scaffold for Src kinases in NALCN channel function. Channels (Austin), 3 (3): 161-3. [PMID:19535918]
8. Yu FH, Catterall WA. (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE, 2004 (253): re15. [PMID:15467096]
Database page citation:
Sodium leak channel, non-selective. Accessed on 28/02/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=126.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Other ion channels. Br J Pharmacol. 172: 5942-5955.