HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Am J Physiol Cell Physiol 292: C1147-C1155, 2007. First published October 25, 2006; doi:10.1152/ajpcell.00598.2005
0363-6143/07 $8.00

This Article Free upon publication Full Text Full Text (PDF) All Versions of this Article: 292/3/C1147    most recent 00598.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Yu, X. Articles by Zhou, Z. Search for Related Content PubMed PubMed Citation Articles by Yu, X. Articles by Zhou, Z.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Calcium influx through I_f channels in rat ventricular myocytes

¹Institute of Molecular Medicine and State Key Laboratory of Biomembrane Engineering, Peking University, Beijing, ²Department of Physiology, Third Military Medical University, Chongqing, ³College of Life Sciences, Peking University, Beijing, ⁴Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital of Fudan University, Shanghai, and ⁵Department of Physiology, Zhejiang University School of Medicine, Hangzhou, China; and ⁶Departments of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia

Submitted 1 December 2005 ; accepted in final form 9 October 2006

The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac (I_f)/neuronal (I_h) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and I_h channels in neurons. This raises the possibility of Ca²⁺ permeation in I_f, the I_h counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca²⁺ signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by I_f in rat ventricular myocytes. We observed Ca²⁺ influx when HCN/I_f channels were activated. Ca²⁺ influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an I_f channel blocker, inhibited I_f and Ca²⁺ influx at the same time. Quantitative analysis revealed that Ca²⁺ flux contributed to 0.5% of current produced by the HCN2 channel or I_f. The associated increase in Ca²⁺ influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which I_f current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca²⁺ chelator), preactivation of I_f channels significantly reduced the action potential duration, and the effect was blocked by another selective I_f channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of I_f channels had no effects on action potential duration. Our data extend our previous discovery of Ca²⁺ influx in I_h channels in neurons to I_f channels in cardiac myocytes.

calcium ion flux; hyperpolarization-activated, cyclic nucleotide-gated/cardiac time- and volume-dependent cation current channels

This article has been cited by other articles:

				H. Cheng and W. J. Lederer Calcium Sparks Physiol Rev, October 1, 2008; 88(4): 1491 - 1545. [Abstract] [Full Text] [PDF]

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]

				G. Michels, M. C. Brandt, N. Zagidullin, I. F. Khan, R. Larbig, S. van Aaken, J. Wippermann, and U. C. Hoppe Direct evidence for calcium conductance of hyperpolarization-activated cyclic nucleotide-gated channels and human native If at physiological calcium concentrations Cardiovasc Res, June 1, 2008; 78(3): 466 - 475. [Abstract] [Full Text] [PDF]