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Mechanism of vagally-mediated atrial tachyarrhythmia in isolated canine right atria
A26
Abstracts,
ISHR Japanese
Section
19th Annual
Meeting
P-6
o Inouc, Tomoko Ohkusa, Tomoko Nao, Tomo Yuji Hisamatsu, Masafumi Yano, Mastmori Mature, C~~ovasc~~ Medicine, ~~~~~ University Medicine, Ube, ~~~c~, Japan
~a~~oto, Division School
of of
Differences in the ~s~butio~ of gap junctions are considered to be an important factor in the otigin of reentrant arrhytbrnias. We investigated the alterations in cardiac connexin (Cx)43 expression and the relation of mech~o~~sduc~o~ during rapid elecbicd stim~a~~ @Es) of contraction in ctthnred ventricuiar ~~o~y~~tes front neonatal rats. ~eth~s and Results: Contraction was induced by RES (3.0 Hz) Cx43 expression was assessed and an i~~~~st~he~~ study was also performed. suited in increases in the expressions of Cx43 proiein and its s~tistic~ significance being achieved after 90 min in the ‘(1.2sO.22 vs 0.86+0.18, w.01). and after 60 min in the latter (1.2510.49 vs 0.67rtO.11, p<.Ol). There was a marked increase in the amount of Cx43 ~~o~active signal. The level of activated protein kinases @RK) increased (2.1+1.1-fold vs control, pc.05) Jun N&-terminal kinases (JNK) peaks being at 15 mm (3.&1.6fold, pc.01). Activation of p38 es ($38) was rapid, with a peak at 5 Olin (6.§*1.0-fo!d, p<.Ol). Angiotensiu II (AGIl) expression increased almost 2-fold. The increase in Cx43 expression was sig~~c~~y atten~ted upon addition of losartan. The increases iu activated BRK, JNK and ~38 were also markedly blocked by lossrtan. c us: RBS-induced increases in AGII content and activated cause a marked upregnlation of Cx43. elevation of Cx43 may result in abnormal cell-to-cell co~~ca~o~ and alterations in the elec~opbysiolo~c properties of ~r~orny~~es, leading to the origin of reentrant arrhythmias. AGII receptor ~~go~st interferes with the MAPKs signalinduction and Cx43 ex~essio~ and may represent a useful eom~~ent to arrhythmia ~erapy.
P-8
in the cardiac mwclr, the gap junction greatly contributes to a site of electrical cell-to-cell coupling and IO a pathway of large molecules between cells. Tbesc physiological functions depend on open or close of the chaunels, and tnnnber of channels which constitute the gap junction. These characleristics of the channel are possibly resulted from phosphoryla~on of the connexins which compose the channd. This stndy was focused to phosphorylatjon of the connexin 43 (Cx43) using ventricular tissue isolated from the adult guinea-pig heart in relation to the physiological function. Cell ~o~u~~atiou was evaluated by intercellular electrical resistance. Phospl~o~lation of Cx43 aud expression of CxQ were evaluated by i~~oblot (Western) and il~uno~st~h~~s~, respectively, using manse monoclonal anti cx43 antibody. Results: Pi-acti~,ation (induced by BBrorno-cyclic AMP or PK4 activator) augmented phosphorylation of Cx43, promoted electrical id-IO-Cdl COUpling, increased i~~noreactive area and imm~or~activit~ of particles of (2x43 at the intercalated disk. PKCactivation (induced by TPA) augmented phosphorylation of Cx43 but inhibited electrical cell-to-cell coupling, and reduced expression of Cx43 at the beak-jnnctio~ part of the intercalated disk and increased ii on the stu-f~ce of the cell. PKC activation inhibited PK.4 dependent phosphorylation of Cx43. Summary: Cx43 is up-regnlatcd by PICA activation and downregulated by PKC activation. (2x43 phospho~lated by PKC may easily be led to dqmdation by proteolysis. The loss of cell communication modulated by PKC activation is disadvantageous to i.ntercellular impulse conduction, however, may be a merit for ischemic pr~~on~tio~u~ due to prevention of diffusion of toxic substances produced during longlasting ischemia into neighboring cells.
Yuko Iwata, Yuki ~t~osaka~, Zhu Shijun, and unekaztt ~~g~kawa. Dept. of Molecular P~ysioIogy~ National ~~diovascuI~ Center research Institute, Suita, Japan *JST omestic Research Fellow De~cien~y of delt~sar~o~ycan, a component of the dystrophin~ycopro~in complex, causes c~iomyopa~y and skeletal muscle dystmphy in B1014.6 hamsters. Using natured myotubes ~t~pared from muscle of normal and ~IOl4.6 hamsters (30-40 day old), we investigated the ~ssibility that the S-sarcoglycan deficiency may lead to alteration in calcium homeostasis which only B1014.6 ad to myocyte damage. lating ~~~1Iular Car’ Ga*‘, su~esting that these ?a’+ influx into B1014.6 myotubes under resting conditions was si~~c~~y h tol.8-fold at 5 mm) than in controls and it was further ac response to cell stretch. hen these cells were subjected to cyclic eIo~gation of up to 20% for lh, a marked increase in release into the medium were creatine ~ho~~o~nase and ruthenium red (5 pM) reduced obsereved GdCl3 (1 45&Z+ e. Ade~o~iral transfer of the 6sarcogl n gene to B1014.6 myotubes abolished ab~o~I calcium horneo~as~s and stitch-educed CK release. The ’ sed resting 45Caz’influx in B1014.6 myotubes may be due to oh-ac~va~d cation channels creased bas J, Physiol. 281. C690-C~99 ed in these 2001). These i-e a defect in Cast handling is sensible for myccyte damage in this animal mod el of muscular dystmphy.
Abstracts,
ISHR Japanese
Section
19th Annual
Meeting
P-6
o Inouc, Tomoko Ohkusa, Tomoko Nao, Tomo Yuji Hisamatsu, Masafumi Yano, Mastmori Mature, C~~ovasc~~ Medicine, ~~~~~ University Medicine, Ube, ~~~c~, Japan
~a~~oto, Division School
of of
Differences in the ~s~butio~ of gap junctions are considered to be an important factor in the otigin of reentrant arrhytbrnias. We investigated the alterations in cardiac connexin (Cx)43 expression and the relation of mech~o~~sduc~o~ during rapid elecbicd stim~a~~ @Es) of contraction in ctthnred ventricuiar ~~o~y~~tes front neonatal rats. ~eth~s and Results: Contraction was induced by RES (3.0 Hz) Cx43 expression was assessed and an i~~~~st~he~~ study was also performed. suited in increases in the expressions of Cx43 proiein and its s~tistic~ significance being achieved after 90 min in the ‘(1.2sO.22 vs 0.86+0.18, w.01). and after 60 min in the latter (1.2510.49 vs 0.67rtO.11, p<.Ol). There was a marked increase in the amount of Cx43 ~~o~active signal. The level of activated protein kinases @RK) increased (2.1+1.1-fold vs control, pc.05) Jun N&-terminal kinases (JNK) peaks being at 15 mm (3.&1.6fold, pc.01). Activation of p38 es ($38) was rapid, with a peak at 5 Olin (6.§*1.0-fo!d, p<.Ol). Angiotensiu II (AGIl) expression increased almost 2-fold. The increase in Cx43 expression was sig~~c~~y atten~ted upon addition of losartan. The increases iu activated BRK, JNK and ~38 were also markedly blocked by lossrtan. c us: RBS-induced increases in AGII content and activated cause a marked upregnlation of Cx43. elevation of Cx43 may result in abnormal cell-to-cell co~~ca~o~ and alterations in the elec~opbysiolo~c properties of ~r~orny~~es, leading to the origin of reentrant arrhythmias. AGII receptor ~~go~st interferes with the MAPKs signalinduction and Cx43 ex~essio~ and may represent a useful eom~~ent to arrhythmia ~erapy.
P-8
in the cardiac mwclr, the gap junction greatly contributes to a site of electrical cell-to-cell coupling and IO a pathway of large molecules between cells. Tbesc physiological functions depend on open or close of the chaunels, and tnnnber of channels which constitute the gap junction. These characleristics of the channel are possibly resulted from phosphoryla~on of the connexins which compose the channd. This stndy was focused to phosphorylatjon of the connexin 43 (Cx43) using ventricular tissue isolated from the adult guinea-pig heart in relation to the physiological function. Cell ~o~u~~atiou was evaluated by intercellular electrical resistance. Phospl~o~lation of Cx43 aud expression of CxQ were evaluated by i~~oblot (Western) and il~uno~st~h~~s~, respectively, using manse monoclonal anti cx43 antibody. Results: Pi-acti~,ation (induced by BBrorno-cyclic AMP or PK4 activator) augmented phosphorylation of Cx43, promoted electrical id-IO-Cdl COUpling, increased i~~noreactive area and imm~or~activit~ of particles of (2x43 at the intercalated disk. PKCactivation (induced by TPA) augmented phosphorylation of Cx43 but inhibited electrical cell-to-cell coupling, and reduced expression of Cx43 at the beak-jnnctio~ part of the intercalated disk and increased ii on the stu-f~ce of the cell. PKC activation inhibited PK.4 dependent phosphorylation of Cx43. Summary: Cx43 is up-regnlatcd by PICA activation and downregulated by PKC activation. (2x43 phospho~lated by PKC may easily be led to dqmdation by proteolysis. The loss of cell communication modulated by PKC activation is disadvantageous to i.ntercellular impulse conduction, however, may be a merit for ischemic pr~~on~tio~u~ due to prevention of diffusion of toxic substances produced during longlasting ischemia into neighboring cells.
Yuko Iwata, Yuki ~t~osaka~, Zhu Shijun, and unekaztt ~~g~kawa. Dept. of Molecular P~ysioIogy~ National ~~diovascuI~ Center research Institute, Suita, Japan *JST omestic Research Fellow De~cien~y of delt~sar~o~ycan, a component of the dystrophin~ycopro~in complex, causes c~iomyopa~y and skeletal muscle dystmphy in B1014.6 hamsters. Using natured myotubes ~t~pared from muscle of normal and ~IOl4.6 hamsters (30-40 day old), we investigated the ~ssibility that the S-sarcoglycan deficiency may lead to alteration in calcium homeostasis which only B1014.6 ad to myocyte damage. lating ~~~1Iular Car’ Ga*‘, su~esting that these ?a’+ influx into B1014.6 myotubes under resting conditions was si~~c~~y h tol.8-fold at 5 mm) than in controls and it was further ac response to cell stretch. hen these cells were subjected to cyclic eIo~gation of up to 20% for lh, a marked increase in release into the medium were creatine ~ho~~o~nase and ruthenium red (5 pM) reduced obsereved GdCl3 (1 45&Z+ e. Ade~o~iral transfer of the 6sarcogl n gene to B1014.6 myotubes abolished ab~o~I calcium horneo~as~s and stitch-educed CK release. The ’ sed resting 45Caz’influx in B1014.6 myotubes may be due to oh-ac~va~d cation channels creased bas J, Physiol. 281. C690-C~99 ed in these 2001). These i-e a defect in Cast handling is sensible for myccyte damage in this animal mod el of muscular dystmphy.