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Voltage-Gated Sodium Channels
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Na_v1.5

Previous and Unofficial Names h1 skm II cardiac sodium channel Nav1.5 Structural Information Species TM P Loops AA Chromosomal Location Gene Name Reference Human 24 4 2016 3p21 SCN5A Rat 24 4 2019 8q32 Scn5a 129-130 Mouse 24 4 2020 9 F3-F4 Scn5a

Contents: Previous and Unofficial Names Structural Information 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 Clinically-Relevant Mutations Biologically Significant Variants

Database Links
ChEMBL Target	11480 (Hs), 12606 (Rn)
Ensembl	ENSG00000183873 (Hs), ENSMUSG00000032511 (Mm), ENSRNOG00000015049 (Rn)
Entrez Gene	6331 (Hs), 20271 (Mm), 25665 (Rn)
GeneCards	SCN5A (Hs)
HomoloGene	22738 (Hs)
OMIM	600163 (Hs)
PharmGKB Gene	PA304 (Hs)
Protein Ontology (PRO)	PRO:000002101 (Hs)
RefSeq Nucleotide	NM_198056 (Hs), NM_000335 (Hs), NM_001099404 (Hs), NM_001099405 (Hs), NM_021544 (Mm), NM_013125 (Rn)
RefSeq Protein	NP_932173 (Hs), NP000326 (Hs), NP_001092874 (Hs), NP_001092875 (Hs), NP_067519 (Mm), NP_037257 (Rn)
UniGene Hs.	517898 (Hs)
UniProt	Q14524 (Hs), P15389 (Rn)
Wikipedia	Nav1.5

Search for 3D structures on the PDB
Search using keywords: Voltage-Gated Sodium Channels Nav1.5	Search using accession numbers: P15389 || Q14524

Associated Proteins
Heteromeric Pore-forming Subunits Name References Not determined	Auxiliary Subunits Name References β4 131-133 β3 131-132,134-135 β2 131-132,136 β1 131-132,135,137-139	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 - 37 HEK-293, tsA-201 Rat Inactivation  60.4 - 37 Comments  Cs aspartate as the major intracellular solute.
V0.5 (mV)  τ (msec)  Reference  Cell type  Species  Activation  -44.0 - 127 HEK 293 cells Human Inactivation  -87.0 - 127 Comments  Cs fluoride as major intracellular solute
V0.5 (mV)  τ (msec)  Reference  Cell type  Species  Activation  -41.0 - 128 HEK 293 cells Rat Inactivation  -89.0 - 128

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 -140.0 142-143 batrachotoxin Rn 7.6 pKd - Physiological 145 veratridine Rn 6.3 pEC50 - -30.0 150
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 (Leiurus quinquestriatus) Rn 7.7 pKd - Physiological 50 ATX-II Hs 7.3 pEC50 - -80.0 27 AFT-II Hs 7.2 pEC50 - -80.0 27 Bc-III Hs 6.5 pEC50 - -80.0 27
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 - -80.0 128,149 tetrodotoxin Rn 5.8 pKd - -80.0 128,149 lidocaine Hs 4.8 pKd - -70.0 – -55.0 146 amiodarone Rn 5.7 pIC50 - Physiological 144 quinidine Rn 4.4 – 5.0 pIC50 - Physiological 147-148 lidocaine Rn 4.2 pIC50 - Physiological 147
View species-specific pore blocker tables

Tissue Distribution
Developing skeletal muscle. Species:  Rat Technique:  Northern Blot References:  129
Heart (intercalated disks in ventricular myocytes). Species:  Rat Technique:  Immunohistochemistry References:  167
Heart. Species:  Mouse Technique:  Immunohistochemistry References:  24,132

Physiological Functions
Action potential generation and conduction. Species:  Human Tissue:  Heart References:  140-141
Action potential generation and conduction. Species:  Mouse Tissue:  Heart References:  24,130

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:  140

Clinically-Relevant Mutations
Disease:  Brugada Syndrome OMIM:  601144 Role:  Nav1.5 is the site of mutations in Brugada Syndrome Type 1, and inherited cardiac arrhythmia. Drugs:  Treated with sodium channel blocking antiarrhythmic drugs References:  151 Click column headers to sort Type Species Molecular location Reference Missense Human A1924T 152 Missense Human Y1795H 153 Missense Human T1620M 151 Missense Human R1512W 152 Missense Human G1262S 154 Missense Human R1232W 151 Missense Human R1193Q 155-156 Missense Human E1053K 157 Missense Human A735V 155 Missense Human R367H 155 Truncation Human W1421X 158
Disease:  Long QT Syndrome, type 3 OMIM:  603830 Role:  Nav1.5 is the site of mutations in long QT Syndrome type 3, an inherited cardic arrhythmia. Drugs:  Treated with mexiletine and other sodium channel-blocking antiarrhythmic gruds. References:  141 Click column headers to sort Type Species Molecular location Reference Deletion Human K1505-P1506-Q1507 141 Missense Human R1826H 159 Missense Human Y1795C 153 Missense Human E1784K 160-161 Missense Human R1664H 162 Missense Human R1623Q 163 Missense Human N1325S 162 Missense Human A997S 159 Missense Human S941N 164
Disease:  Lenègre's disease OMIM:  113900 Role:  Loss-of-function mutations in Nav1.5 leads to this inherited cardiac conduction failure. References:  140 Click column headers to sort Type Species Molecular location Reference Deletion Human Exon 22 (IVS22DS+2 T-C) 165 Frameshift Human A1771+ 165 Missense Human D1595N 166 Missense Human G298S 166

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:  NP000326  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:

To cite this receptor data page, please use the following:

William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-Gated Sodium Channels: Na_v1.5. Last modified on 2010-07-01. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=582.

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