TY - JOUR
T1 - Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat
AU - Du, Yuan
AU - Huang, Xin
AU - Wang, Tingzhong
AU - Han, Ke
AU - Zhang, Junbo
AU - Xi, Yutao
AU - Wu, Geru
AU - Ma, Aiqun
PY - 2007/6
Y1 - 2007/6
N2 - Sodium current INa plays an important role in the pacemaker activity of the sinoatrial node (SAN). However, expression profiles of corresponding sodium channel subunits in normal SAN remain unclear. And little is known about expression alteration of sodium channel in SAN under heart failure (HF) condition. We assessed SAN function and expression of Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6, and Nav1.7 in sham-operated rats and rats subjected to abdominal arteriovenous shunt (volume overload)-induced HF. Immunohistochemistry, Western blot, and quantitative real-time reverse transcriptase PCR analysis were used to quantify sodium channel subunit protein and mRNA expression in the SAN. Intrinsic heart rate declined and sinus node recovery time was prolonged in HF rats, indicating suppressed SAN pacemaker function. In rat SAN, Nav1.1 and Nav1.6 were the primary subunits, Nav1.5 and Nav1.7 were weakly expressed, and Nav1.2 and Nav1.3 were not found to be present. HF significantly decreased SAN sodium channel expression at both the protein and mRNA levels (Nav1.1 by 61 and 71%, Nav1.6 by 49 and 46%, respectively). In conclusion, Nav1.1 and Nav1.6 are the dominant subunits in rat SAN, and downregulation of Nav1.1 and Nav1.6 expression contributes to HF-induced SAN dysfunction. These findings provide additional information about molecular basis of disease-related impairment of SAN function.
AB - Sodium current INa plays an important role in the pacemaker activity of the sinoatrial node (SAN). However, expression profiles of corresponding sodium channel subunits in normal SAN remain unclear. And little is known about expression alteration of sodium channel in SAN under heart failure (HF) condition. We assessed SAN function and expression of Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6, and Nav1.7 in sham-operated rats and rats subjected to abdominal arteriovenous shunt (volume overload)-induced HF. Immunohistochemistry, Western blot, and quantitative real-time reverse transcriptase PCR analysis were used to quantify sodium channel subunit protein and mRNA expression in the SAN. Intrinsic heart rate declined and sinus node recovery time was prolonged in HF rats, indicating suppressed SAN pacemaker function. In rat SAN, Nav1.1 and Nav1.6 were the primary subunits, Nav1.5 and Nav1.7 were weakly expressed, and Nav1.2 and Nav1.3 were not found to be present. HF significantly decreased SAN sodium channel expression at both the protein and mRNA levels (Nav1.1 by 61 and 71%, Nav1.6 by 49 and 46%, respectively). In conclusion, Nav1.1 and Nav1.6 are the dominant subunits in rat SAN, and downregulation of Nav1.1 and Nav1.6 expression contributes to HF-induced SAN dysfunction. These findings provide additional information about molecular basis of disease-related impairment of SAN function.
KW - Heart failure
KW - Laser capture microdissection
KW - Pacemaker current
KW - Sinoatrial node
KW - Sodium channel
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U2 - 10.1007/s00424-007-0216-4
DO - 10.1007/s00424-007-0216-4
M3 - Article
C2 - 17273863
AN - SCOPUS:34248354261
SN - 0031-6768
VL - 454
SP - 451
EP - 459
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
IS - 3
ER -