TY - JOUR
T1 - Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes
AU - Zeevi-Levin, Naama
AU - Barac, Yaron D.
AU - Reisner, Yotam
AU - Reiter, Irina
AU - Yaniv, Gal
AU - Meiry, Gideon
AU - Abassi, Zaid
AU - Kostin, Sawa
AU - Schaper, Jutta
AU - Rosen, Michael R.
AU - Resnick, Nitzan
AU - Binah, Ofer
N1 - Funding Information:
This work was supported by the Israel Science Foundation, the Minerva Foundation through the Bernard Katz Center for Cell Biophysics, the Rappaport Institute, the Israeli Ministry of Health, and the US–Israel Binational Foundation, and the Max Planck Society, Germany.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - Objectives: Altered gap junctional coupling of ventricular myocytes plays an important role in arrhythmogenesis in ischemic heart disease. Since hypoxia is a major component of ischemia, we tested the hypothesis that hypoxia causes gap junctional remodeling accompanied by conduction disturbances. Methods: Cultured neonatal rat ventricular myocytes were exposed to hypoxia (1% O 2) for 15 min to 5 h, connexin43 (Cx43) expression was analyzed, and conduction velocity was measured using the Micro-Electrode Array data acquisition system. Results: After 15 min of hypoxia, conduction velocity was unaffected, while total Cx43, including the phosphorylated and nonphosphorylated isoforms, was increased. After 5 h of hypoxia, total Cx43 protein was decreased by 50%, while the nonphosphorylated Cx43 isoform was unchanged. Confocal analyses yielded a 55% decrease in the gap junctional Cx43 fluorescence signal, a 55% decrease in gap junction number, and a 26% decrease in size. The changes in Cx43 were not accompanied by changes in mRNA levels. The reduction in Cx43 protein levels was associated with a ∼20% decrease in conduction velocity compared to normoxic cultures. Conclusions: Short-term hypoxia (5 h) decreases Cx43 protein and conduction velocity, thereby contributing to the generation of an arrhythmogenic substrate.
AB - Objectives: Altered gap junctional coupling of ventricular myocytes plays an important role in arrhythmogenesis in ischemic heart disease. Since hypoxia is a major component of ischemia, we tested the hypothesis that hypoxia causes gap junctional remodeling accompanied by conduction disturbances. Methods: Cultured neonatal rat ventricular myocytes were exposed to hypoxia (1% O 2) for 15 min to 5 h, connexin43 (Cx43) expression was analyzed, and conduction velocity was measured using the Micro-Electrode Array data acquisition system. Results: After 15 min of hypoxia, conduction velocity was unaffected, while total Cx43, including the phosphorylated and nonphosphorylated isoforms, was increased. After 5 h of hypoxia, total Cx43 protein was decreased by 50%, while the nonphosphorylated Cx43 isoform was unchanged. Confocal analyses yielded a 55% decrease in the gap junctional Cx43 fluorescence signal, a 55% decrease in gap junction number, and a 26% decrease in size. The changes in Cx43 were not accompanied by changes in mRNA levels. The reduction in Cx43 protein levels was associated with a ∼20% decrease in conduction velocity compared to normoxic cultures. Conclusions: Short-term hypoxia (5 h) decreases Cx43 protein and conduction velocity, thereby contributing to the generation of an arrhythmogenic substrate.
KW - Arrhythmia
KW - Connexins
KW - Gap junctions
KW - Hypoxia
KW - Myocytes
UR - http://www.scopus.com/inward/record.url?scp=20144382861&partnerID=8YFLogxK
U2 - 10.1016/j.cardiores.2005.01.014
DO - 10.1016/j.cardiores.2005.01.014
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C2 - 15769449
AN - SCOPUS:20144382861
SN - 0008-6363
VL - 66
SP - 64
EP - 73
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -
