原创力文档the “funny” current (if) inhibition by ivabradine at membrane potentials encompassing spontaneous depolarization in pacemaker cells当前u201c有趣的u201d(如果)抑制ivabradine在起搏细胞的膜电位包括自发的去极化.pdfVIP
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the “funny” current (if) inhibition by ivabradine at membrane potentials encompassing spontaneous depolarization in pacemaker cells当前u201c有趣的u201d(如果)抑制ivabradine在起搏细胞的膜电位包括自发的去极化
Molecules 2012, 17, 8241-8254; doi:10.3390/molecule
OPEN ACCESS
molecules
ISSN 1420-3049
/journal/molecules
Article
The “Funny” Current (I ) Inhibition by Ivabradine at
f
Membrane Potentials Encompassing Spontaneous
Depolarization in Pacemaker Cells
Yael Yaniv, Victor A. Maltsev, Bruce D. Ziman, Harold A. Spurgeon and Edward G. Lakatta *
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging,
NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA
* Author to whom correspondence should be addressed; E-Mail: LakattaE@;
Tel.: +1-410-558-8202; Fax: +1-410-558-8150.
Received: 21 May 2012; in revised form: 3 July 2012 / Accepted: 4 July 2012 /
Published: 9 July 2012
Abstract: Recent clinical trials have shown that ivabradine (IVA), a drug that inhibits the
funny current (I ) in isolated sinoatrial nodal cells (SANC), decreases heart rate and
f
reduces morbidity and mortality in patients with cardiovascular diseases. While IVA
inhibits I , this effect has been reported at essentially unphysiological voltages, i.e., those
f
more negative than the spontaneous diastolic depolarization (DD) between action
potentials (APs). We tested the relative potency of IVA to block If over a wide range of
membrane potentials, including those that encompass DD governing t
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