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Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes.
J Mol Cell Cardiol. 2014 Jan; 66:53-62.JM

Abstract

Pulmonary veins (PVs) are believed to be a crucial origin of atrial fibrillation. We recently reported that rat PV cardiomyocytes exhibit arrhythmogenic automaticity in response to norepinephrine. Herein, we further characterized the electrophysiological properties underlying the potential arrhythmogenicity of PV cardiomyocytes. Patch clamping studies revealed a time dependent hyperpolarization-activated inward current in rat PV cardiomyocytes, but not in left atrial (LA) myocytes. The current was Cs(+) resistant, and was not affected by removal of external Na(+) or K(+). The current was inhibited with Cd(2+), and the reversal potential was sensitive to changes in [Cl(-)] on either side of the membrane in a manner consistent with a Cl(-) selective channel. Cl(-) channel blockers attenuated the current, and slowed or completely inhibited the norepinephrine-induced automaticity. The biophysical properties of the hyperpolarization-activated Cl(-) current in rat PVs were different from those of ClC-2 currents previously reported: (i) the voltage-dependent activation of the Cl(-) current in rat PVs was shifted to negative potentials as [Cl(-)]i increased, (ii) the Cl(-) current was enhanced by extracellular acidification, and (iii) extracellular hyper-osmotic stress increased the current, whereas hypo-osmotic cell swelling suppressed the current. qPCR analysis revealed negligible ClC-2 mRNA expression in the rat PV. These findings suggest that rat PV cardiomyocytes possess a peculiar voltage-dependent Cl(-) channel, and that the channel may play a functional role in norepinephrine-induced automaticity.

Authors+Show Affiliations

Department of Cell Physiology, Akita University Graduate School of Medicine, Akita, Japan.Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.Department of Cell Physiology, Akita University Graduate School of Medicine, Akita, Japan.Department of Cell Physiology, Akita University Graduate School of Medicine, Akita, Japan. Electronic address: onok@med.akita-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24239603

Citation

Okamoto, Yosuke, et al. "Pathological Impact of Hyperpolarization-activated Chloride Current Peculiar to Rat Pulmonary Vein Cardiomyocytes." Journal of Molecular and Cellular Cardiology, vol. 66, 2014, pp. 53-62.
Okamoto Y, Kawamura K, Nakamura Y, et al. Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes. J Mol Cell Cardiol. 2014;66:53-62.
Okamoto, Y., Kawamura, K., Nakamura, Y., & Ono, K. (2014). Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes. Journal of Molecular and Cellular Cardiology, 66, 53-62. https://doi.org/10.1016/j.yjmcc.2013.11.002
Okamoto Y, et al. Pathological Impact of Hyperpolarization-activated Chloride Current Peculiar to Rat Pulmonary Vein Cardiomyocytes. J Mol Cell Cardiol. 2014;66:53-62. PubMed PMID: 24239603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes. AU - Okamoto,Yosuke, AU - Kawamura,Koichi, AU - Nakamura,Yuta, AU - Ono,Kyoichi, Y1 - 2013/11/12/ PY - 2013/06/27/received PY - 2013/10/28/revised PY - 2013/11/04/accepted PY - 2013/11/19/entrez PY - 2013/11/19/pubmed PY - 2014/8/19/medline KW - 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid KW - 9-AC KW - 9-anthracene carboxylic acid KW - AF KW - Atrial fibrillation KW - Ca(2+) activated Cl(−) channel KW - Cl(−) channel KW - Cm KW - DIDS KW - GAPDH KW - I(ClCa) KW - I(K1) KW - I(KH) KW - I(f) KW - I(ti) KW - LA KW - NE KW - PV KW - Pulmonary vein KW - atrial fibrillation KW - cell membrane capacitance KW - glyceraldehyde-3-phosphate dehydrogenase KW - hyperpolarization-activated K(+) current KW - hyperpolarization-activated cation current KW - inward-rectifier K(+) current KW - left atrium KW - norepinephrine KW - pulmonary vein KW - qPCR KW - quantitative polymerase chain reaction KW - transient inward current SP - 53 EP - 62 JF - Journal of molecular and cellular cardiology JO - J Mol Cell Cardiol VL - 66 N2 - Pulmonary veins (PVs) are believed to be a crucial origin of atrial fibrillation. We recently reported that rat PV cardiomyocytes exhibit arrhythmogenic automaticity in response to norepinephrine. Herein, we further characterized the electrophysiological properties underlying the potential arrhythmogenicity of PV cardiomyocytes. Patch clamping studies revealed a time dependent hyperpolarization-activated inward current in rat PV cardiomyocytes, but not in left atrial (LA) myocytes. The current was Cs(+) resistant, and was not affected by removal of external Na(+) or K(+). The current was inhibited with Cd(2+), and the reversal potential was sensitive to changes in [Cl(-)] on either side of the membrane in a manner consistent with a Cl(-) selective channel. Cl(-) channel blockers attenuated the current, and slowed or completely inhibited the norepinephrine-induced automaticity. The biophysical properties of the hyperpolarization-activated Cl(-) current in rat PVs were different from those of ClC-2 currents previously reported: (i) the voltage-dependent activation of the Cl(-) current in rat PVs was shifted to negative potentials as [Cl(-)]i increased, (ii) the Cl(-) current was enhanced by extracellular acidification, and (iii) extracellular hyper-osmotic stress increased the current, whereas hypo-osmotic cell swelling suppressed the current. qPCR analysis revealed negligible ClC-2 mRNA expression in the rat PV. These findings suggest that rat PV cardiomyocytes possess a peculiar voltage-dependent Cl(-) channel, and that the channel may play a functional role in norepinephrine-induced automaticity. SN - 1095-8584 UR - https://www.unboundmedicine.com/medline/citation/24239603/Pathological_impact_of_hyperpolarization_activated_chloride_current_peculiar_to_rat_pulmonary_vein_cardiomyocytes_ DB - PRIME DP - Unbound Medicine ER -