在豬隻心房顫動模式中,奇趣電流通道在蛋白、訊息核醣核酸及組織學層次之變化
Other Title
Changes of the Funny (Pacemaker) Current Channels at Protein,
mRNA and Histology Levels in a porcine Model of Atrial Fibrillation
mRNA and Histology Levels in a porcine Model of Atrial Fibrillation
Date Issued
2002
Date
2002
Author(s)
賴凌平
DOI
902314B002227
Abstract
There are two specific aims in the present
study.
1. To investigate the distribution of funny
current channels in different part of
atrial tissue.
2. To investigate the changes of funny
current channels in a porcine model of
atrial fibrillation.
Funny current is a hyperpolarization
activated current. It contributes to the
spontaneous depolarization in phase 4 of
action potential and it plays important roles
in the generation of normal sinus rhythm. In
our past studies, we have shown that the 2
mRNA level of funny current channels is
increased in human subjects with atrial
fibrillation. However, information regarding
the changes in protein and histological levels
are not available. Therefore, we propose to
use the porcine model of atrial fibrillation to
investigate the distribution of funny current
channels as well as its changes in atrial
fibrillation.
First, we established a porcine model of
atrial fibrillation. A transvenous AOO
pacemaker was implanted in adult pigs. The
pacing rate was set at 600 per minute. After
pacing for 4 weeks, the pacemaker was
turned off and the pig developed persistent
atrial fibrillation. The pigs were sacrificed
two week after turning off the pacemaker and
atrial tissues were collected. We obtained
atrial tissue from the following positions:
right atrial appendage, right atrial free wall,
left atrial appendage, left atrial free wall, AV
node, atrial tissue extending into the
pulmonary veins. With the above-obtained
tissue, we performed Western blotting
analysis, reverse transcription-polymerase
chain reaction, and immunohistochemical
studies.
Our results showed that the funny
current channel protein was present in the
pulmonary venous tissue. The channel
protein was evenly distributed in the atrial
tissue. We also found that the amount of
funny current channel protein was not
significantly different between pigs with
atrial fibrillation and control pigs. In
immunohistochemitry studies, the AV nodal
tissue showed reaction with the antibody as
expected. However, the funny current
channel protein in the atrial tissue was
strongly associated with vascular smooth
muscle. The pulmonary venous tissue was
alos studied. It showed diffuse mild reaction
with the funny current channel antibody. In
RT-PCR experiments, we failed to amplify
the funny current channel RNA because the
funny current cDNA sequence was not
available in the GenBank and human primers
did not work on the porcine model.
In conclusion, our study demonstrated
for the first time the distribution of funny
current channel in the atrial and pulmonary
venous tissues. We found that funny current
channels existed not only in pacemaker
tissues but also working atrial myocardial
tissue. This channel was also present in the
pulmonary venous tissue. We also showed
that the funny current channel was present in
large amount in the vascular smooth muscle
cells. This finding is also novel. It is possible
that these channels also play important roles
in smooth muscle contraction.
Subjects
Atrial fibrillation
funny current
channel
channel
Publisher
臺北市:國立臺灣大學醫學院內科
Type
report
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