Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat.
BACKGROUND
The electrical activity of the atrioventricular node (AVN) is functionally heterogeneous, but how this relates to distinct cell types and the 3-dimensional structure of the AVN is unknown. To address this, we have studied the expression of Na(V)1.5 and other Na+ channel isoforms in the AVN.


RESULTS
The rat AVN was identified by Masson's trichrome staining together with immunolabeling of marker proteins: connexin40, connexin43, desmoplakin, atrial natriuretic peptide, and hyperpolarization-activated and cyclic nucleotide-gated channel 4. Na+ channel expression was investigated with immunohistochemistry with isoform-specific Na+ channel antibodies. Na(V)1.1 was distributed in a similar manner to Na(V)1.5. Na(V)1.2 was not detected. Na(V)1.3 labeling was present in nerve fibers and cell bodies (but not myocytes) and was abundant in the penetrating atrioventricular (AV) bundle and the common bundle but was much less abundant in other regions. Na(V)1.5 labeling was abundant in the atrial and ventricular myocardium and the left bundle branch. Na(V)1.5 labeling was absent in the open node, penetrating AV bundle, AV ring bundle, and common bundle but present at a reduced level in the inferior nodal extension and transitional zone. Na(V)1.6 was not detected.


CONCLUSIONS
Our findings provide molecular evidence of multiple electrophysiological cell types at the AV junction. Impaired AV conduction as a result of mutations in or loss of Na(V)1.5 must be the result of impaired conduction in the AVN inputs (inferior nodal extension and transitional zone) or output (bundle branches) rather than the AVN itself (open node and penetrating AV bundle).
Yoo
Shin
S
Cardiovascular Research Group, School of Medicine, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, United Kingdom.
Dobrzynski
Halina
H
Fedorov
Vadim V
VV
Xu
Shang-Zhong
SZ
Yamanushi
Tomoko T
TT
Jones
Sandra A
SA
Yamamoto
Mitsuru
M
Nikolski
Vladmir P
VP
Efimov
Igor R
IR
Boyett
Mark R
MR
D000818:Animals; D001283:Atrioventricular Node / Q000737:chemistry*; D002036:Bundle of His / Q000737:chemistry; D006325:Heart Atria / Q000737:chemistry; D006352:Heart Ventricles / Q000737:chemistry; D008297:Male; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000737:chemistry; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009412:Nerve Fibers / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000032:analysis*; D014261:Tricuspid Valve / Q000737:chemistry
D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062554:NAV1.5 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568250:Scn1a protein, rat; C568253:Scn2A protein, rat; C478638:Scn3a protein, rat; C568322:Scn5a protein, rat; C507811:Scn8a protein, rat; D015222:Sodium Channels