Proceedings of the XXXVI International Congress Of
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Volume 59 · Supplement 1 · 2009 Volume 59 · Supplement 1 · 2009 The XXXVI International Congress of Volume 59 · Supplement 59 Volume 1 · 2009 · pp 1–XX Physiological Sciences (IUPS2009) International Scientific Program Committees (ISPC) ISPC Chair Yoshihisa Kurachi Vice Chair Ole Petersen ISPC from IUPS Council Akimichi Kaneko (IUPS President) Irene Schulz (IUPS Vice President) Pierre Magistretti (IUPS Vice President) Malcolm Gordon (IUPS Treasurer) ISPC IUPS2009 Members and Associated Members Proceedings of the XXXVI International Congress of Physiological Sciences (IUPS2009) Commission I Locomotion Commission VII Comparative Physiology: Hans Hoppeler, Masato Konishi, Hiroshi Nose Evolution, Adaptation & Environment Function of Life: Elements and Integration Commission II Circulation/Respiration Malcolm Gordon, Ken-ichi Honma, July 27–August 1, 2009, Kyoto, Japan Yung Earm, Makoto Suematsu, Itsuo Kodama Kazuyuki Kanosue Commission III Endocrine, Reproduction & Commission VIII Genomics & Biodiversity Development David Cook, Hideyuki Okano, Gozoh Tsujimoto Caroline McMillen, Yasuo Sakuma, Toshihiko Yada Commission IX Others Commission IV Neurobiology Ann Sefton, Peter Hunter, Osamu Matsuo, Quentin Pittman, Harunori Ohmori, Fumihiko Kajiya, Tadashi Isa, Tadaharu Tsumoto, Megumu Yoshimura Jun Tanji Commission V Secretion & Absorption Local Executives Irene Schulz, Miyako Takaki, Yoshikatsu Kanai Yasuo Mori, Ryuji Inoue Commission VI Molecular & Cellular Biology Cecilia Hidalgo, Yoshihiro Kubo, Katsuhiko Mikoshiba, Masahiro Sokabe, Yukiko Gotoh P1AM-1-1 P1AM-1-2 FAMILIALISOLATEDCARDIACCONDUCTIONDEFECT THEEFFECTSOFINTERCELLULARELECTRICAL ASSOCIATEDWITHAMUTATIONINTHECONNEXIN40 UNCOUPLINGONTHEDYNAMICSOFSPIRAL GENEGJA5 REENTRYINVENTRICULARMYOCARDIUMOF Naomasa Makita1, Naokata Sumitomo2, Akiko Seki3, Nobuhisa Hagiwara3, ISOLATEDRABBITHEARTS Jean-Jacques Schott4, Hiroyuki Tsutsui1 Yoshio Takemoto1, Tomoyuki Suzuki1, Sara Kato1, Hiroki Takanari1, 1Department of Cardiovascular Medicine, Hokkaido University Graduate Mikio Morishima1, Yusuke Okuno1, Masahide Harada1, Haruo Honjo1, 2 School of Medicine, Japan, Department of Pediatrics and Child Health, Nihon 2 1 1 3 Ichiro Sakuma , Kaichiro Kamiya , Itsuo Kodama University School of Medicine, Tokyo, Japan, Department of Cardiology, Tokyo 1 4 Department of Cardiovascular Research, Research Institute of Environmental Women’s Medical University, Tokyo, Japan, INSERM U915, l'institut du thorax, 2 Medichine, Nagoya University, Japan, Graduate School of Engineering, Nantes, France University of Tokyo, Japan Isolated cardiac conduction defect (ICCD) is a hereditary lethal arrhythmia, characterized Background: Gap junction (GJ) remodeling associated with heart diseases increases the risk by slow conduction in the specialized conduction system without underlying structural heart of life-threatening ventricular tachyarrhythmia (ventricular fibrillation /tachycardia: VF/VT), diseases. We have genetically screened gap junction (GJ) genes for 139 ICCD probands. In but underlying mechanisms remain unclear. one ICCD family with two sudden death victims, we found a missense mutation Q58L in We investigated the effects of intercellular uncoupling on the dynamics of spiral-wave connexin40 (Cx40), a GJ predominantly expressed in the atrium and His-Purkinje system. (SW) reentry, which is the principle mechanism of VF/VT. Methods: Optical action The mutation carriers showed identical ECG of idioventricular rhythm and complete left potential signals were recorded from ventricles of Langendorff-perfused rabbit hearts. bundle branch block. GFP-tagged Q58L Cx40 transfected in GJ-deficient N2A cells showed Results: Inhibition of GJ channels by carbenoxolone (CBX, 30 μM) significantly decreased predominant expression in the intracellular space and impaired GJ formation. Intracellularly conduction velocity (by 26.4±9.0 %, n=11) and the space constant (by 35.7±7.9 % n=7) applied dye Lucifer yellow was readily transferred to the neighboring cells in wild type (WT), without affecting action potential duration. SW reentry in controls showed meandering along but its transfer was delayed in the Q58L. Furthermore, junctional conductance measured a functional block line (FBL, 5.80±0.42 mm, n=6). After CBX infusion, a stationary rotor by the dual whole-cell patch clamp was severely impaired in Q58L cell pairs (12.9±5.8 nS circulated around shorter FBL (1.74±0.16 mm, n=6). The incidence of sustained reentry for WT (n=4) vs. 1.2±0.7 nS for Q58L (n=5); p<0.01), suggesting that the genetic defect of episodes (>30 s) significantly increased from 22/73 to 53/67 after CBX, and average VT GJA5 disrupts cell-to-cell communication in the atrium and His-Purkinje system, leading to cycle length significantly increased from 132±12 ms to 149±23 ms (n=25, p<0.0001). manifest ICCD. In conclusion, present study has provided the first demonstration that GJA5 Conclusions: Intercellular electrical uncoupling of ventricular myocardium by inhibition of is the responsible gene for familiar ICCD. GJ channels stabilizes SW reentry in favor of its persistence. P1AM-1-3 P1AM-1-4 REGIONALHETEROGENEITYOFCONNEXIN-43 GENERATIONOFTHEELECTROCARDIOGRAPHIC COUPLINGPROMOTESSUSCEPTIBILITYTO TWAVEANDBODYSURFACEPOTENTIAL REENTRANTARRHYTHMIASINRATCULTURED DISTRIBUTIONINFROGSANDPIKES MYOCYTEMONOLAYERS Marina Vaykshnorayte, Jan Azarov Hideo Tanaka, Takuo Nakagami, Tetsuro Takamatsu Laboratory of Cardiac Physiology, Institute of PhysiologyKomi Science Department of Pathology and cell Regulation, Kyoto Prefectural University Center, Urals Branch Division, Russian Academy of Sciences, Russia of Medicine, Japan The amphibian and the fish heart presents a convenient model to study the T wave Although altered connexin43 (Cx43) expression is known to promote genesis genesis as it has the only ventricle and hence the contributions of apex-to-base of tachyarrhythmias, precise mechanism of Cx43 remodeling underlying and transmural repolarization gradients can be compared. Potential mapping was arrhythmogenesis is unknown. To address this we studied changes in impulse done on eight pikes and nine frogs using 32 body surface, 24 epicardial and 40-72 propagation of confluent monolayers of neonatal rat cultured myocytes under intramural unipolar leads. The distribution of repolarization durations in frog and inhibition of intercellular coupling by dominant-negative (DN) Cx43 via adenoviral pike myocardium was similar for that the ARIs were shorter at the apex than at vector-mediated gene transfer for DNCx43-fused red fluorescence protein (RFP). A the base and that the largest transmural ARI gradient was found in the base and high-resolution fluorescence microscopy was used to visualize both the fluo4- and decreased toward the apex. However, the directions of the transmural gradients RFP-fluorescence intensities for measurements of Ca2+-transient propagation and were opposite: in pikes, the repolarization sequence proceeded from endocardial DNCx43 distribution, respectively. DNCx43 inhibition of the monolayers produced slowing of Ca2+ transient conduction velocity and preferential emergence of spiral- -to-epicardial, in frogs - epicardial-to-endocardial. Cardiac electric field on the wave reentrant arrhythmias. The monolayers showed regional conduction slowing and body surface correlated with the epicardial sequences of repolarization as well as subsequent generation of wave break, resulting in reentrant arrhythmias. Higher RFP with the potential distributions on the ventricular epicardium. The body surface fluorescence intensity was detected at the wave-break point than at the surrounding potential distributions during the T wave in both animal species studied were myocardium, indicating a culprit role of DNCx43 inhibition in the genesis of reentry. quite close to each other in spite of opposite transmural repolarization gradients In conclusion, regional heterogeneity in gap-junctional communication produces a providing evidence in support of the major role of apex-to-base repolarization wave break of conduction, leading to reentrant arrhythmias. pattern in the generation of the electrocardiographic T wave in pikes and frogs. P1AM-1-5 P1AM-1-6 CARDIACTISSUESLICESFROMGUINEA-PIGHEARTS DIACYLGLYCEROL KINASE ζ RESTORES Gαq- ASASUITABLEMODELFORPHARMACOLOGICAL INDUCEDATRIALSTRUCTURALREMODELINGIN ANDPHYSIOLOGICALINVESTIGATIONS TRANSGENICMICE Alexandra Bussek1, Erich Wettwer1, Horst Lohmann2, Patrizia Camelliti3, Masamichi Hirose1, Yasuchika Takeishi2, Hisashi Shimojo3, 1 Ursula Ravens Takeshi Niizeki4, Tsutomu Nakada1, Isao Kubota1, Mitsuhiko Yamada1 1Pharmacology und Toxicology, Dresden University of Technology, Germany, 1 2 3 Department of Molecular Pharmacology, Shinshu University, Japan, Lohmann Neuropharmacological Consulting, Germany, Department of 2First Department of Internal Medicine, Fukushima Medical School, Physiology, Anatomy and Genetics, University of Oxford, UK Japan, 3Department of Pathology, Shinshu University, Japan, 4Cardiology, We established a cardiac tissue slice model from adult guinea-pig hearts for Pulmonology, and Nephrology, Yamagata University, Japan electrophysiological and pharmacological investigations. Cell orientation in living Previous study showed that diacylglycerol kinase ζ (DGKζ), which degenerates slices was studied in relation to the direction of the primary cutting plane. diacylglycerol (DAG), inhibits ventricular structural remodeling and rescues activated G Vertical and horizontal transmural and tangential slices (0.45 mm thick) were prepared