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Nav1.5

Family: Voltage-gated sodium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Activators
Gating Inhibitors
Pore Blockers
Tissue Distribution
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 24 4 2016 3p21 SCN5A sodium channel, voltage-gated, type V, alpha subunit
Mouse 24 4 2020 9 F3-F4 Scn5a sodium channel, voltage-gated, type V, alpha
Rat 24 4 2019 8q32 Scn5a sodium channel, voltage-gated, type V, alpha subunit 9,24
Previous and Unofficial Names
h1
skm II
cardiac sodium channel
Nav1.5
SkM II
CMD1E
LQT3
HB1
HBBD
PFHB1
IVF
HB2
HH1
SSS1
CDCD2
CMPD2
ICCD
sodium channel, voltage-gated, type V, alpha (long QT syndrome 3)
long QT syndrome 3
SCAL
sodium channel protein cardiac muscle subunit alpha
sodium channel protein type 5 subunit alpha
sodium channel protein type V subunit alpha
sodium channel, voltage-gated, type 5, alpha subunit
sodium channel, voltage-gated, type V, alpha
sodium channel, voltage-gated, type V, alpha polypeptide
voltage-gated sodium channel Nav1.5c
voltage-gated sodium channel subunit alpha Nav1.5
Nav1.5c
mH1
SkM2
Database Links
ChEMBL Target
DrugBank Target
Ensembl
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProt
Wikipedia
Search for 3D structures on the PDB
Search by keyword: Voltage-gated sodium channels Nav1.5
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
β4 6,11,17
β3 6-7,10-11
β2 6,11,44
β1 2,6,10-11,15,45
Other Associated Proteins
Name References
Not determined
Associated Protein Comments
Subunit associations are based on co-localization, co-expression in heterologous cells, and co-immunoprecipitation. No biochemical data on Nav1.5 purified from cardiac tissue are available.
Ion Selectivity and Conductance Comments
Single channel conductance for Nav1.5 is ~20 pS and is not reported to be depended on species [1956,2884,2885]
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  25.9 - 16 HEK-293, tsA-201 Rat
Inactivation  60.4 - 16
Comments  Cs aspartate as the major intracellular solute.
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -44.0 - 30 HEK 293 cells Human
Inactivation  -87.0 - 30
Comments  Cs fluoride as major intracellular solute
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -41.0 - 43 HEK 293 cells Rat
Inactivation  -89.0 - 43
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
aconitine Hs - - 3x10-5 - 1x10-4 -140.0 19,42
batrachotoxin Rn 7.6 pKd - Physiological 31
veratridine Rn 6.3 pEC50 - -30.0 36
View species-specific activator tables
Gating inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
α-scorpion toxin Rn 7.7 pKd - Physiological 25
ATX-II Hs 7.3 pEC50 - -80.0 22
AFT-II Hs 7.2 pEC50 - -80.0 22
Bc-III Hs 6.5 pEC50 - -80.0 22
View species-specific gating inhibitor tables
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
saxitoxin Rn 7.4 pKd - -80.0 5,43
tetrodotoxin Rn 5.8 pKd - -80.0 5,43
lidocaine Hs 4.8 pKd - -70.0 – -55.0 21
amiodarone Rn 5.7 pIC50 - Physiological 33
quinidine Rn 4.4 – 5.0 pIC50 - Physiological 8,32
lidocaine Rn 4.2 pIC50 - Physiological 8
View species-specific pore blocker tables
Tissue Distribution
Heart.
Species:  Mouse
Technique:  Immunohistochemistry
References:  11-12
Developing skeletal muscle.
Species:  Rat
Technique:  Northern Blot
References:  9
Heart (intercalated disks in ventricular myocytes).
Species:  Rat
Technique:  Immunohistochemistry
References:  4
Physiological Functions
Action potential generation and conduction.
Species:  Human
Tissue:  Heart
References:  27,40
Action potential generation and conduction.
Species:  Mouse
Tissue:  Heart
References:  12,24
Physiological Consequences of Altering Gene Expression
The SCN5A -/+ mouse shows a phenotype resembling Lenègre's disease, including age-related lengthening of the P-wave and PR- and QRS-interval duration.
Species:  Mouse
Tissue:  Heart
Technique:  Various
References:  27
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0002972 abnormal cardiac muscle contractility PMID: 11972032 
Scn5atm1Pec Scn5atm1Pec/Scn5atm1Pec
involves: Swiss
MGI:98251  MP:0001544 abnormal cardiovascular system physiology PMID: 11533705 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0001629 abnormal heart rate PMID: 11972032 
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0005294 abnormal heart ventricle morphology PMID: 11972032 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0003137 abnormal impulse conducting system conduction PMID: 11972032 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0003137 abnormal impulse conducting system conduction PMID: 11533705 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0003137 abnormal impulse conducting system conduction PMID: 15809371 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0003137 abnormal impulse conducting system conduction PMID: 16403066 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0003137 abnormal impulse conducting system conduction PMID: 17145985 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0004215 abnormal myocardial fiber physiology PMID: 11972032 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0004215 abnormal myocardial fiber physiology PMID: 16403066 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0004215 abnormal myocardial fiber physiology PMID: 17145985 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0006142 abnormal sinoatrial node conduction PMID: 17145985 
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0004067 abnormal trabecula carnea morphology PMID: 11972032 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0010505 abnormal T wave PMID: 11533705 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0003141 cardiac fibrosis PMID: 15809371 
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0001698 decreased embryo size PMID: 11972032 
Scn5atm1Clhh Scn5atm1Clhh/Scn5atm1Clhh
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0001698 decreased embryo size PMID: 16403066 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0005333 decreased heart rate PMID: 11533705 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0005333 decreased heart rate PMID: 15809371 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0005333 decreased heart rate PMID: 17145985 
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0004567 decreased myocardial fiber number PMID: 11972032 
Scn5atm1Agrc Scn5atm1Agrc/Scn5atm1Agrc
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0006207 embryonic lethality during organogenesis PMID: 11972032 
Scn5atm1Pec Scn5atm1Pec/Scn5atm1Pec
involves: Swiss
MGI:98251  MP:0006207 embryonic lethality during organogenesis PMID: 11533705 
Scn5atm1Clhh Scn5atm1Clhh/Scn5atm1Clhh
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0006207 embryonic lethality during organogenesis PMID: 16403066 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 16403066 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0001636 irregular heartbeat PMID: 11533705 
Scn5atm1Clhh Scn5atm1Clhh/Scn5atm1Clhh
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0001636 irregular heartbeat PMID: 16403066 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0001636 irregular heartbeat PMID: 16403066 
Scn5atm1Clhh Scn5atm1Clhh/Scn5atm1Clhh
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0001651 necrosis PMID: 16403066 
Scn5atm1(SCN5A)Rdn Scn5atm1(SCN5A)Rdn/Scn5atm1(SCN5A)Rdn
involves: 129S6/SvEvTac
MGI:98251  MP:0002169 no abnormal phenotype detected PMID: 17083109 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0002082 postnatal lethality PMID: 16403066 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0002083 premature death PMID: 11533705 
Scn5atm1Care Scn5atm1Care/Scn5atm1Care
FVB.129P2-Scn5a
MGI:98251  MP:0002080 prenatal lethality PMID: 17145985 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0003896 prolonged PR interval PMID: 11972032 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0003896 prolonged PR interval PMID: 15809371 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0003896 prolonged PR interval PMID: 17145985 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0004071 prolonged P wave PMID: 11972032 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0004071 prolonged P wave PMID: 15809371 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0010392 prolonged QRS complex duration PMID: 15809371 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0010392 prolonged QRS complex duration PMID: 17145985 
Scn5a+|Scn5atm1Pec Scn5atm1Pec/Scn5a+
involves: Swiss
MGI:98251  MP:0003233 prolonged QT interval PMID: 11533705 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv
MGI:98251  MP:0003233 prolonged QT interval PMID: 15809371 
Scn5a+|Scn5atm1Care Scn5atm1Care/Scn5a+
FVB.129P2-Scn5a
MGI:98251  MP:0003233 prolonged QT interval PMID: 17145985 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0002064 seizures PMID: 16403066 
Scn5a+|Scn5atm1Agrc Scn5atm1Agrc/Scn5a+
involves: 129/Sv * C57BL/6J
MGI:98251  MP:0008950 ventricular tachycardia PMID: 11972032 
Scn5a+|Scn5atm1Clhh Scn5atm1Clhh/Scn5a+
involves: 129 * 129S/SvEv * C57BL/6J
MGI:98251  MP:0008950 ventricular tachycardia PMID: 16403066 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cardiomyopathy, dilated, 1E; CMD1E
OMIM: 
Orphanet: 
References: 
Mutations not determined
Disease:  Atrial cardiomyopathy with heart block
OMIM: 
Orphanet: 
References: 
Mutations not determined
Disease:  Brugada Syndrome
OMIM: 
Orphanet: 
Role: 
Drugs: 
References:  3
Click column headers to sort
Type Species Molecular location Description Reference
Missense Human A1924T 26
Missense Human Y1795H 23
Missense Human T1620M 3
Missense Human R1512W 26
Missense Human G1262S 34
Missense Human R1232W 3
Missense Human R1193Q 35,38
Missense Human E1053K 18
Missense Human A735V 35
Missense Human R367H 35
Truncation Human W1421X 20
Disease:  Long QT Syndrome, type 3
OMIM: 
Orphanet: 
Role: 
Drugs: 
References:  40
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human K1505-P1506-Q1507 40
Missense Human R1826H 1
Missense Human Y1795C 23
Missense Human E1784K 13,41
Missense Human R1664H 39
Missense Human R1623Q 14
Missense Human N1325S 39
Missense Human A997S 1
Missense Human S941N 29
Disease:  Lenègre's disease
OMIM: 
Orphanet: 
Role: 
References:  27
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human Exon 22 (IVS22DS+2 T-C) 28
Frameshift Human A1771+ 28
Missense Human D1595N 37
Missense Human G298S 37
Disease:  Ventricular fibrillation during myocardial infarction, susceptibility to
OMIM: 
Orphanet: 
References: 
Mutations not determined
Disease:  Sick sinus syndrome 1, autosomal recessive; SSS1
OMIM: 
Orphanet: 
References: 
Mutations not determined
Disease:  Atrial fibrillation, familial, 10; ATFB10
OMIM: 
Orphanet: 
References: 
Mutations not determined
Biologically Significant Variants
Isoform d
Nucleotide accession:  NM_001099405 
Protein accession:  NP_001092875 
Amino acids:  1998
Type:  Splice variant
Species:  Human
References: 
Isoform c
Nucleotide accession:  NM_001099404 
Protein accession:  NP_001092874 
Amino acids:  2016
Type:  Splice variant
Species:  Human
References: 
Isoform b
Nucleotide accession:  NM_000335 
Protein accession:  NP_000326 
Amino acids:  2015
Type:  Splice variant
Species:  Human
References: 
Isoform a
Nucleotide accession:  NM_198056 
Protein accession:  NP_932173 
Amino acids:  2016
Type:  Splice variant
Species:  Human
References: 

REFERENCES

To cite this database page, please use the following:

William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Nav1.5. Last modified on 01/03/2012. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=582.


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