Downregulation of neuronal sodium channel subunits Nav1.1 and Nav1.6 in the sinoatrial node from volume-overloaded heart failure rat.
Sodium current I(Na) 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.
Du
Yuan
Y
Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, Shaanxi, 710061, China.
Huang
Xin
X
Wang
Tingzhong
T
Han
Ke
K
Zhang
Junbo
J
Xi
Yutao
Y
Wu
Geru
G
Ma
Aiqun
A
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000378:metabolism* / Q000473:pathology; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C568250:Scn1a protein, rat; C507811:Scn8a protein, rat; D015222:Sodium Channels