Connexin40-deficient mice exhibit atrioventricular nodal and infra-Hisian conduction abnormalities.
BACKGROUND
Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Purkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of deficiencies in Cx40.


RESULTS
Ten Cx40-/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40-/- mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6+/-6.4 msec vs 36.0+/-4.1 msec, P = 0.002). Not only the HV interval (14.0+/-3.0 msec vs 10.4+/-1.2 msec, P = 0.003) but also the AH interval (33.2+/-4.8 msec vs 27.1+/-3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40-/- compared with Cx40+/+ mice.


CONCLUSIONS
Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction.
VanderBrink
B A
BA
Cardiac Arrhythmia Service, New England Medical Center, Boston, Massachusetts 02111, USA.
Sellitto
C
C
Saba
S
S
Link
M S
MS
Zhu
W
W
Homoud
M K
MK
Estes
N A
NA
Paul
D L
DL
Wang
P J
PJ
D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology*; D002036:Bundle of His / Q000503:physiopathology*; D017630:Connexins / Q000172:deficiency* / Q000235:genetics; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D011930:Reaction Time; D012016:Reference Values; D012032:Refractory Period, Electrophysiological; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein