Interventricular differences in sodium current and its potential role in Brugada syndrome
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Interventricular differences in sodium current and its potential role in Brugada syndrome. / Calloe, Kirstine; Aistrup, Gary L.; Di Diego, José M.; Goodrow, Robert J.; Treat, Jacqueline A.; Cordeiro, Jonathan M.
In: Physiological Reports, Vol. 6, No. 14, e13787, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Interventricular differences in sodium current and its potential role in Brugada syndrome
AU - Calloe, Kirstine
AU - Aistrup, Gary L.
AU - Di Diego, José M.
AU - Goodrow, Robert J.
AU - Treat, Jacqueline A.
AU - Cordeiro, Jonathan M.
PY - 2018
Y1 - 2018
N2 - Brugada syndrome (BrS) is an inherited disease associated with ST elevation in the right precordial leads, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults. Mutations in the cardiac sodium channel account for a large fraction of BrS cases. BrS manifests in the right ventricle (RV), which led us to examine the biophysical and molecular properties of sodium channel in myocytes isolated from the left (LV) and right ventricle. Patch clamp was used to record sodium current (INa) in single canine RV and LV epicardial (epi) and endocardial (endo) myocytes. Action potentials were recorded from multicellular preparations and single cells. mRNA and proteins were determined using quantitative RT-PCR and Western blot. Although LV wedge preparations were thicker than RV wedges, transmural ECG recordings showed no difference in the width of the QRS complex or transmural conduction time. Action potential characteristics showed RV epi and endo had a lower Vmax compared with LV epi and endo cells. Peak INa density was significantly lower in epi and endo RV cells compared with epi and endo LV cells. Recovery from inactivation of INa in RV cells was slightly faster and half maximal steady-state inactivation was more positive. β2 and β4 mRNA was detected at very low levels in both ventricles, which was confirmed at the protein level. Our observations demonstrate that Vmax and Na+ current are smaller in RV, presumably due to differential Nav1.5/β subunit expression. These results provide a potential mechanism for the right ventricular manifestation of BrS.
AB - Brugada syndrome (BrS) is an inherited disease associated with ST elevation in the right precordial leads, polymorphic ventricular tachycardia (PVT), and sudden cardiac death in adults. Mutations in the cardiac sodium channel account for a large fraction of BrS cases. BrS manifests in the right ventricle (RV), which led us to examine the biophysical and molecular properties of sodium channel in myocytes isolated from the left (LV) and right ventricle. Patch clamp was used to record sodium current (INa) in single canine RV and LV epicardial (epi) and endocardial (endo) myocytes. Action potentials were recorded from multicellular preparations and single cells. mRNA and proteins were determined using quantitative RT-PCR and Western blot. Although LV wedge preparations were thicker than RV wedges, transmural ECG recordings showed no difference in the width of the QRS complex or transmural conduction time. Action potential characteristics showed RV epi and endo had a lower Vmax compared with LV epi and endo cells. Peak INa density was significantly lower in epi and endo RV cells compared with epi and endo LV cells. Recovery from inactivation of INa in RV cells was slightly faster and half maximal steady-state inactivation was more positive. β2 and β4 mRNA was detected at very low levels in both ventricles, which was confirmed at the protein level. Our observations demonstrate that Vmax and Na+ current are smaller in RV, presumably due to differential Nav1.5/β subunit expression. These results provide a potential mechanism for the right ventricular manifestation of BrS.
KW - Action Potentials
KW - left ventricle
KW - patch clamp
KW - right ventricle
KW - sodium current
U2 - 10.14814/phy2.13787
DO - 10.14814/phy2.13787
M3 - Journal article
C2 - 30009404
AN - SCOPUS:85050824398
VL - 6
JO - Physiological Reports
JF - Physiological Reports
SN - 2051-817X
IS - 14
M1 - e13787
ER -
ID: 201909252