Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation
Loss-of-function (LOF) variants in SCN1B, encoding the voltage-gated sodium channel β1/β1B subunits, are linked to neurological and cardiovascular diseases. Scn1b-null mice have spontaneous seizures and ventricular arrhythmias and die by approximately 21 days after birth. β1/β1B Subunits play critical roles in regulating the excitability of ventricular cardiomyocytes and maintaining ventricular rhythmicity. However, whether they also regulate atrial excitability is unknown. We used neonatal Scn1b-null mice to model the effects of SCN1B LOF on atrial physiology in pediatric patients. Scn1b deletion resulted in altered expression of genes associated with atrial dysfunction. Scn1b-null hearts had a significant accumulation of atrial collagen, increased susceptibility to pacing induced atrial fibrillation (AF), sinoatrial node (SAN) dysfunction, and increased numbers of cholinergic neurons in ganglia that innervate the SAN. Atropine reduced the incidence of AF in null animals. Action potential duration was prolonged in null atrial myocytes, with increased late sodium current density and reduced L-type calcium current density. Scn1b LOF results in altered atrial structure and AF, demonstrating the critical role played by Scn1b in atrial physiology during early postnatal mouse development. Our results suggest that SCN1B LOF variants may significantly impact the developing pediatric heart.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
JCI insight - 7(2022), 10 vom: 23. Mai |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ramos-Mondragon, Roberto [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 24.05.2022 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1172/jci.insight.152050 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341263362 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341263362 | ||
| 003 | DE-627 | ||
| 005 | 20231226011357.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/jci.insight.152050 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1137.xml |
| 035 | |a (DE-627)NLM341263362 | ||
| 035 | |a (NLM)35603785 | ||
| 035 | |a (PII)e152050 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ramos-Mondragon, Roberto |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.05.2022 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Loss-of-function (LOF) variants in SCN1B, encoding the voltage-gated sodium channel β1/β1B subunits, are linked to neurological and cardiovascular diseases. Scn1b-null mice have spontaneous seizures and ventricular arrhythmias and die by approximately 21 days after birth. β1/β1B Subunits play critical roles in regulating the excitability of ventricular cardiomyocytes and maintaining ventricular rhythmicity. However, whether they also regulate atrial excitability is unknown. We used neonatal Scn1b-null mice to model the effects of SCN1B LOF on atrial physiology in pediatric patients. Scn1b deletion resulted in altered expression of genes associated with atrial dysfunction. Scn1b-null hearts had a significant accumulation of atrial collagen, increased susceptibility to pacing induced atrial fibrillation (AF), sinoatrial node (SAN) dysfunction, and increased numbers of cholinergic neurons in ganglia that innervate the SAN. Atropine reduced the incidence of AF in null animals. Action potential duration was prolonged in null atrial myocytes, with increased late sodium current density and reduced L-type calcium current density. Scn1b LOF results in altered atrial structure and AF, demonstrating the critical role played by Scn1b in atrial physiology during early postnatal mouse development. Our results suggest that SCN1B LOF variants may significantly impact the developing pediatric heart | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Arrhythmias | |
| 650 | 4 | |a Cardiology | |
| 650 | 4 | |a Mouse models | |
| 650 | 4 | |a Sodium channels | |
| 650 | 7 | |a SCN1B protein, human |2 NLM | |
| 650 | 7 | |a Scn1b protein, mouse |2 NLM | |
| 650 | 7 | |a Voltage-Gated Sodium Channel beta-1 Subunit |2 NLM | |
| 700 | 1 | |a Edokobi, Nnamdi |e verfasserin |4 aut | |
| 700 | 1 | |a Hodges, Samantha L |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shuyun |e verfasserin |4 aut | |
| 700 | 1 | |a Bouza, Alexandra A |e verfasserin |4 aut | |
| 700 | 1 | |a Canugovi, Chandrika |e verfasserin |4 aut | |
| 700 | 1 | |a Scheuing, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Juratli, Lena |e verfasserin |4 aut | |
| 700 | 1 | |a Abel, William R |e verfasserin |4 aut | |
| 700 | 1 | |a Noujaim, Sami F |e verfasserin |4 aut | |
| 700 | 1 | |a Madamanchi, Nageswara R |e verfasserin |4 aut | |
| 700 | 1 | |a Runge, Marschall S |e verfasserin |4 aut | |
| 700 | 1 | |a Lopez-Santiago, Luis F |e verfasserin |4 aut | |
| 700 | 1 | |a Isom, Lori L |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JCI insight |d 2016 |g 7(2022), 10 vom: 23. Mai |w (DE-627)NLM257703918 |x 2379-3708 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2022 |g number:10 |g day:23 |g month:05 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/jci.insight.152050 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2022 |e 10 |b 23 |c 05 | ||