Molecular Characterization of the Hyperpolarization-activated Cation Channel in Rabbit Heart Sinoatrial Node*

  1. Harunori Ohmori§
  1. From the Department of Physiology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan

Abstract

We cloned a cDNA (HAC4) that encodes the hyperpolarization-activated cation channel (I for I h) by screening a rabbit sinoatrial (SA) node cDNA library using a fragment of rat brainI f cDNA. HAC4 is composed of 1150 amino acid residues, and its cytoplasmic N- and C-terminal regions are longer than those of HAC1–3. The transmembrane region of HAC4 was most homologous to partially cloned mouse I f BCNG-3 (96%), whereas the C-terminal region of HAC4 showed low homology to all HAC family members so far cloned. Northern blotting revealed that HAC4 mRNA was the most highly expressed in the SA node among the rabbit cardiac tissues examined. The electrophysiological properties of HAC4 were examined using the whole cell patch-clamp technique. In COS-7 cells transfected with HAC4 cDNA, hyperpolarizing voltage steps activated slowly developing inward currents. The half-maximal activation was obtained at −87.2 ± 2.8 mV under control conditions and at −64.4 ± 2.6 mV in the presence of intracellular 0.3 mm cAMP. The reversal potential was −34.2 ± 0.9 mV in 140 mm Na+ oand 5 mm K+ o versus 10 mm Na+ i and 145 mmK+ i. These results indicate that HAC4 formsI f in rabbit heart SA node.

Footnotes

  • * This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to M. T., A. N., and H. O.) and by a Japan Heart Foundation research grant (to T. M. I).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AB022927.

  • These two authors contributed equally to this work.

  • § To whom correspondence should be addressed. Tel.: 81-75-753-4351; Fax: 81-75-753-4349; E-mail: ohmori{at}med.kyoto-u.ac.jp.

  • Abbreviations:
    If
    hyperpolarization-activated cation channel(s)
    SA
    sinoatrial
    • Received December 24, 1998.
    • Revision received February 10, 1999.
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