[Expression and function of voltage-gated Na+ channel isoforms in rat sinoatrial node].
OBJECTIVE
To detect the expression of voltage-gated Na(+) channel (NaCh) isoforms in rat sinoatrial node and explore their functions.


METHODS
Expressions of NaCh isoforms Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6 and Nav1.7 in the rat sinoatrial node were detected by immunohistochemistry. The functional roles of the NaChs were tested by observing the effect of tetrodotoxin, a specific blocker of NaChs, on the intrinsic heart rate of isolated rat working heart.


RESULTS
The tetrodotoxin- sensitive neuronal isoforms Nav1.1, Nav1.6 and Nav1.7 as well as the tetrodotoxin-resistant cardiac isoform Nav1.5 were present in the rat sinoatrial node, and the neuronal isoforms were more abundant than Nav1.5 (P<0.05). The selective blockade of tetrodotoxin-sensitive isoforms (presumably Nav1.1, Nav1.6 and Nav1.7) by 100 nmol/L tetrodotoxin scarcely affected the intrinsic heart rate (0.5-/+2.9%, P>0.05) while blockade of tetrodotoxin-resistant isoform (presumably Nav1.5) by 2 micromol/L tetrodotoxin resulted in an obvious decline in the intrinsic heart rate (22.1-/+2.1%, P<0.001).


CONCLUSIONS
Nav1.1, Nav1.5, Nav1.6 and Nav1.7 are all present in rat sinoatrial node. Although neuronal isoforms are more abundant, Nav1.5 seems to contribute more to activity of the sinoatrial node.
Huang
Xin
X
Department of Cardiology, First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Medical School of Xi'an Jiaotong University, Xi'an 710061, China. hearthx@126.com
Ma
Ai-Qun
AQ
Yang
Pei
P
Du
Yuan
Y
Xi
Yu-Tao
YT
Geng
Tao
T
D000818:Animals; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D020033:Protein Isoforms / Q000096:biosynthesis; D051381:Rats; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D015222:Sodium Channels / Q000096:biosynthesis*; D013779:Tetrodotoxin / Q000494:pharmacology
D062550:NAV1.1 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C568250:Scn1a protein, rat; C568322:Scn5a protein, rat; C507811:Scn8a protein, rat; D015222:Sodium Channels; D013779:Tetrodotoxin