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Inhibition of mitochondrial KATP channel can improve conduction delay induced by angiotensin II during early reoxygenation
Journal of Molecular and Cellular Cardiology 46 (2009) 443
Contents lists available at ScienceDirect
Journal of Molecular and Cellular Cardiology j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y j m c c
Abstracts
Additional abstracts from the 25th Annual Meeting of the International Society for Heart Research, Japanese Section, December 5–6, 2008, Yokohama, Japan P-A-6 Axonal guidance for sympathetic neuron to cardiac myocyte by glial cell line-derived neurotrophic factor Keiko Miwa, Jong-Kook Lee, Yoshiko Takagishi, Itsuo Kodama Research Institute of Environmental Medicine, Nagoya University, Japan
P-A-37 Inhibition of mitochondrial KATP channel can improve conduction delay induced by angiotensin II during early reoxygenation Daisuke Wakatsuki, Hisa Shimojima, Yukei Higashi, Hiroshi Suzuki, Youichi Takeyama Division of Cardiology, Showa University Fujigaoka Hospital, Japan
Aim: The aim of the present study is to explore the feasibility of axonal guidance for sympathetic neuron (SNs) to cardiomyocytes (CMs) by glial cell line-derived neurotrophic factor (GDNF). Methods: Sympathetic neuron (SNs) and cardiomyocytes (CMs) were isolated from neonatal rat superior cervical ganglia and hearts, respectively. SNs and CMs were cultured separately in the same dishes at a close distance (1–2 mm) for 120 h. GDNF was either (1) overexpressed in CMs using adenovirus vector (AdGDNF-CM) or (2) added in the culture medium (0.5–10 ng/ml). The densities of axons, synapse and receptors of SNs or CMs were examined using time-lapse imaging, immunofluorescent stains and electron microscopy. Results: (1) When SNs were cultured between AdGDNF-CMs and mock-transfected CMs (mock-CM), most of axons from SNs were projected toward AdGDNF-CMs. The number of axons toward AdGDNF-CMs was significantly larger than that toward mock-CMs (p < 0.01 vs. CONT-CMs, n = 3). (2) When GDNF was added to the culture medium of mock-CMs, the density of neurofilament-M were significantly increased compared to the culture condition without GDNF (CONT) (by 877.5%, p < 0.01 vs. CONT, n = 5). As for synapse formation, GDNF significantly increased synapsin Ipositive termination of SNs over the surface of CMs by 779.1%, compared to CONT (p < 0.05 vs. CONT, n = 5). Electron microscopic observations also revealed typical synapse formation between SNs and CMs in the presence of GDNF. Expression of beta1-adrenergic receptors was significantly increased by 1635.3% with GDNF (10 ng/ml) (p < 0.05 vs. CONT, n = 4). Conclusion: GDNF acts as an axonal guidance cue for sympathetic neuron to cardomyocytes. The results suggest that GDNF may be used as a new molecule to induce cardiac sympathetic innervation. Keywords: Cardiac sympathetic innervation; Axon guidance; Neurotrophins.
Background and objectives: The mitochondrial KATP channel (mitoKATP) opening which can be triggered from activation of angiotensin II type 1 receptor on ischemia/reperfusion causes the ROS-induced ROS release. The electrophysiological actions of angiotensin II (Ang II) linked with the genesis of reperfusion arrhythmias were elucidated by clarifying the roles of Ang II and mitoKATP on cardiac impulse propagation. Methods: Ventricular papillary muscle (PPM, 3mm length) from the rat heart (WKYIzm) were fixed on the superfusion chamber. Membrane action potential, Dv/Dtmax and activation time were recorded at the tip of PPM. Activation times were measured as the interval from stimulus artifact to Dv/Dtmax. After PPM preparations were superfused with ischemic-like solution for 5 min, they were washed out with normal oxygenated Tyrode (control), containing Ang II (10–8 M), or Ang II plus 5-HD (mito KATP blocker; 10–6 M), plus CV-11974 (AT1 receptor blocker; 10–7 M) during 5 min. To assess the excitability, the rapid electrical stimulation (10 Hz) for 60 sec were applied to the preparations just after reoxygenation. Results: Ang II accelerated 2:1 conduction block by the rapid electrical stimulation for 60 sec after reoxygenation. These actions of Ang II were abolished under Ang II plus 5-HD and CV-11974 (p<0.001 vs Ang II). The prolongation of activation time was rapidly recovered under perfusion of Ang II plus 5-HD (p<0.001 vs Ang II) and CV-11974 (p<0.01 vs Ang II) for 5 min after reoxygenation. Conclusion: Mito KATP blocker and AT1 receptor blocker abolished conduction block and conduction delay induced by Ang II. This result demonstrated that mito KATP channnel blocker protectively associated with arrhythmogenesis properties during reoxygenation. Keywords: Mitochondrial KATP channel; Angiotensin II; Reperfusion arrhythmia.
doi:10.1016/j.yjmcc.2008.11.009
doi:10.1016/j.yjmcc.2008.11.020
0022-2828/$ – see front matter pii:S0022-2828(08)01407-7
Contents lists available at ScienceDirect
Journal of Molecular and Cellular Cardiology j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y j m c c
Abstracts
Additional abstracts from the 25th Annual Meeting of the International Society for Heart Research, Japanese Section, December 5–6, 2008, Yokohama, Japan P-A-6 Axonal guidance for sympathetic neuron to cardiac myocyte by glial cell line-derived neurotrophic factor Keiko Miwa, Jong-Kook Lee, Yoshiko Takagishi, Itsuo Kodama Research Institute of Environmental Medicine, Nagoya University, Japan
P-A-37 Inhibition of mitochondrial KATP channel can improve conduction delay induced by angiotensin II during early reoxygenation Daisuke Wakatsuki, Hisa Shimojima, Yukei Higashi, Hiroshi Suzuki, Youichi Takeyama Division of Cardiology, Showa University Fujigaoka Hospital, Japan
Aim: The aim of the present study is to explore the feasibility of axonal guidance for sympathetic neuron (SNs) to cardiomyocytes (CMs) by glial cell line-derived neurotrophic factor (GDNF). Methods: Sympathetic neuron (SNs) and cardiomyocytes (CMs) were isolated from neonatal rat superior cervical ganglia and hearts, respectively. SNs and CMs were cultured separately in the same dishes at a close distance (1–2 mm) for 120 h. GDNF was either (1) overexpressed in CMs using adenovirus vector (AdGDNF-CM) or (2) added in the culture medium (0.5–10 ng/ml). The densities of axons, synapse and receptors of SNs or CMs were examined using time-lapse imaging, immunofluorescent stains and electron microscopy. Results: (1) When SNs were cultured between AdGDNF-CMs and mock-transfected CMs (mock-CM), most of axons from SNs were projected toward AdGDNF-CMs. The number of axons toward AdGDNF-CMs was significantly larger than that toward mock-CMs (p < 0.01 vs. CONT-CMs, n = 3). (2) When GDNF was added to the culture medium of mock-CMs, the density of neurofilament-M were significantly increased compared to the culture condition without GDNF (CONT) (by 877.5%, p < 0.01 vs. CONT, n = 5). As for synapse formation, GDNF significantly increased synapsin Ipositive termination of SNs over the surface of CMs by 779.1%, compared to CONT (p < 0.05 vs. CONT, n = 5). Electron microscopic observations also revealed typical synapse formation between SNs and CMs in the presence of GDNF. Expression of beta1-adrenergic receptors was significantly increased by 1635.3% with GDNF (10 ng/ml) (p < 0.05 vs. CONT, n = 4). Conclusion: GDNF acts as an axonal guidance cue for sympathetic neuron to cardomyocytes. The results suggest that GDNF may be used as a new molecule to induce cardiac sympathetic innervation. Keywords: Cardiac sympathetic innervation; Axon guidance; Neurotrophins.
Background and objectives: The mitochondrial KATP channel (mitoKATP) opening which can be triggered from activation of angiotensin II type 1 receptor on ischemia/reperfusion causes the ROS-induced ROS release. The electrophysiological actions of angiotensin II (Ang II) linked with the genesis of reperfusion arrhythmias were elucidated by clarifying the roles of Ang II and mitoKATP on cardiac impulse propagation. Methods: Ventricular papillary muscle (PPM, 3mm length) from the rat heart (WKYIzm) were fixed on the superfusion chamber. Membrane action potential, Dv/Dtmax and activation time were recorded at the tip of PPM. Activation times were measured as the interval from stimulus artifact to Dv/Dtmax. After PPM preparations were superfused with ischemic-like solution for 5 min, they were washed out with normal oxygenated Tyrode (control), containing Ang II (10–8 M), or Ang II plus 5-HD (mito KATP blocker; 10–6 M), plus CV-11974 (AT1 receptor blocker; 10–7 M) during 5 min. To assess the excitability, the rapid electrical stimulation (10 Hz) for 60 sec were applied to the preparations just after reoxygenation. Results: Ang II accelerated 2:1 conduction block by the rapid electrical stimulation for 60 sec after reoxygenation. These actions of Ang II were abolished under Ang II plus 5-HD and CV-11974 (p<0.001 vs Ang II). The prolongation of activation time was rapidly recovered under perfusion of Ang II plus 5-HD (p<0.001 vs Ang II) and CV-11974 (p<0.01 vs Ang II) for 5 min after reoxygenation. Conclusion: Mito KATP blocker and AT1 receptor blocker abolished conduction block and conduction delay induced by Ang II. This result demonstrated that mito KATP channnel blocker protectively associated with arrhythmogenesis properties during reoxygenation. Keywords: Mitochondrial KATP channel; Angiotensin II; Reperfusion arrhythmia.
doi:10.1016/j.yjmcc.2008.11.009
doi:10.1016/j.yjmcc.2008.11.020
0022-2828/$ – see front matter pii:S0022-2828(08)01407-7