Characterization of the Hyperpolarization-Activated Current, I <sub>f</sub> , in Ventricular Myocytes From Human Failing Heart
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- Elisabetta Cerbai
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Roberto Pino
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Francesco Porciatti
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Guido Sani
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Michele Toscano
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Massimo Maccherini
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Gabriele Giunti
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
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- Alessandro Mugelli
- the Department of Pharmacology, University of Firenze (E.C., R.P., F.P., A.M.); Cardiosurgery, University of Cagliari (G.S.); and Institute of Thoracic and Cardiovascular Surgery, University of Siena (M.T., M.M., G.G.), Italy.
Description
<jats:p> <jats:italic>Background</jats:italic> Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I <jats:sub>f</jats:sub> -like current is expressed in rat left ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I <jats:sub>f</jats:sub> in human LVMs. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> LVMs were isolated from hearts of three male patients undergoing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I <jats:sub>f</jats:sub> , ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244±27 pF (n=25). I <jats:sub>f</jats:sub> occurred in all cells tested; its density measured at −120 mV was 2.1±0.3 pA/pF. Activation curves of I <jats:sub>f</jats:sub> (n=24) were fitted by a Boltzmann function; the threshold was −55 mV; midpoint, −70.9±2.1 mV; slope, −5.4±0.3 mV; and maximal specific conductance, 19.6±2.5 pS/pF. I <jats:sub>f</jats:sub> blockade by extracellular cesium was voltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from −12.7±0.5 to −24.8±2.1 mV and a 64% decrease of current conductance. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> I <jats:sub>f</jats:sub> is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I <jats:sub>f</jats:sub> could be an arrhythmogenic mechanism in patients with severe heart failure. </jats:p>
Journal
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- Circulation
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Circulation 95 (3), 568-571, 1997-02-04
Ovid Technologies (Wolters Kluwer Health)
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Details 詳細情報について
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- CRID
- 1364233270364622720
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- ISSN
- 15244539
- 00097322
- http://id.crossref.org/issn/00097322
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- Data Source
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- Crossref