pulmonary vein, arrhythmogenic coupling
Post on 11-Jul-2015
238 Views
Preview:
TRANSCRIPT
Arrhythmogenic Coupling between Na+-Ca2+ Exchanger and IP3 Receptor in
Rat Pulmonary Vein Cardiomyocyte
Yosuke Okamoto1, Makoto Takano2,
Kouiti Kawamura3, Takayoshi Ohba1,
Kyoichi Ono1.
1Department of Cell Physiology, Akita University Graduate School of Medicine2Department of Physiology, Kurume University School of Medicine, Kurume
3Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine
Haïssaguerre M, Jais P et al. N Engl J Med. (1998) 339: 695-666.
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
http://lifesciencedb.jp/bp3d/
40 μm
4 μm 4 μm
2 μm2 μm 2 μm
4 μm
Nicolas Doisne et al.Am J Physiol Heart Circ Physiol (2009) 297:102-108.
LA
PV
Ventricular Myocyte
Area (µm2)
Cel
ls (
%)
20 μm
LA
PV
500030001000
30
20
10
0
30
20
10
0
50 µm
A
-10
-6
-2
pA/p
F20 40-60
-4
-40 -20
20 m
V
50 ms
PV
LA
pA/pF
mV
-12
-10-8
-6-4-2
2
-120-100 -60 -40 -20
*
*
*
B
100 ms
LA PV
1.0
0.8
0.6
0.4
0.2
0.0-60-40 -20 0 20 40
mV
Ava
ilabi
lity
10 p
A/p
F
*
* **
*
*
C
200 ms
10 p
A/p
F
mV
LA PV
*
40 m
V
1 min
1 min
NE 10μM
40m
V
NE 10 μM
NE 10μM
A
D
B
50 ms 20 m
V
C
50 p
A/p
F40
mV
1 s
Voltage Clamp
-50 mV
40
-40Vm
(m
V)
0.2
0.3
F40
5/F
480
1 S
2 min
NE 10μM
20 m
V
A
B NE 10μM
100
pA40
mV
2 S
Vm (mV)
Cur
rent
(pA
)
-120
-100
-80
-60
-40
-20
-60 -40 -20 20 400I-V Relationship of Arrhythmogenic Inward CurrentsInduced by NE
Na+/Ca2+ Exchanger
40
-40
0.3
0.2
Vm
(m
V)
F40
5/F
480
10 S
SEA 0400 10μM
NE 10μM
Spontaneous Ca2+ releasing after Cessation of Automatic Action Potentials
The Effect of α1 and β1 Antagonists
Prazosin 1μM
1 minAtenolol 5 μM
30 S
40 m
V
NE 10μM
NE 10 μmol/L
Calphostin C 1 μM
40 m
V
U73122 1 μM
2-APB 2 μM
30 S 40 m
V
30 S 40 m
V
2 min
Cascade of α1 signal transduction
Co-localization of Na+/Ca2+ Exchangers and IP3 R
0 1 2 3 4 5 6 7 8 9 10
0 1 2 3 4 5 6 7 8 9 10
0 1 2 3 4 5 6 7 8 9 10
0
10
-10
-20
x105
0
20
-10
10
x104
04
-2-4
x105
8
0 1 2 3 4 5 6 7 8 9 10μm
μm
μm
μm
012
43
103
NCXIP3R
Fluorescence intensity
AutoCorrelation: NCX
CrossCorrelation: NCX vs IP3R
AutoCorrelation: IP3R
10 μm
NCX1
IP3R2
Merge
“Ca2+ release via the IP3R is activated by α1 stimulant, and the Ca2+ in
turn spin up the NCX, which is co-localized with the IP3R, producing
transient depolarization. β1-adrenergic action of NE reinforce CICR,
resulting in Ca2+ overload. The accumulated Ca2+ would be released
again via the IP3R. ”
Okamoto Y et al. J Mol Cell Cardiol. 2012 (in press)
top related