Calcium influx through If channels in rat ventricular myocytes

Xiao Yu, Xiao Wei Chen, Peng Zhou, Lijun Yao, Tao Liu, Bo Zhang, Ying Li, Hui Zheng, Liang Hong Zheng, Claire Xi Zhang, Iain Bruce, Jun Bo Ge, Shi Qiang Wang, Zhi An Hu, Han Gang Yu*, Zhuan Zhou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac (If)/neuronal (Ih) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalentselective channels. Recently we discovered that calcium ions can permeate through HCN4 and If channels in neurons. This raises the possibility of Ca2+ permeation in If, the Ih 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 If in rat ventricular myocytes. We observed Ca2+ influx when HCN/If channels were activated. Ca2+ influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an If channel blocker, inhibited If 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 If. The associated increase in Ca2+ influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which If current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca2+ chelator), preactivation of If channels significantly reduced the action potential duration, and the effect was blocked by another selective If channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of If channels had no effects on action potential duration. Our data extend our previous discovery of Ca2+ influx in Ih channels in neurons to If channels in cardiac myocytes.

Original languageEnglish
Pages (from-to)C1147-C1155
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3
Publication statusPublished - Mar 2007
Externally publishedYes


  • Calcium ion flux
  • Cyclic nucleotide-gated/ cardiac time- and volume-dependent cation current channels
  • Hyperpolarization-activated

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