© 1999 American Heart Association, Inc.
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Distribution and Prevalence of Hyperpolarization-Activated Cation Channel (HCN) mRNA Expression in Cardiac Tissues
From the Institute of Molecular Cardiology (W.S., R.W., H.Y., J.W., R.T.W., J.E.D., D.M., I.S.C.) and Departments of Physiology and Biophysics (W.S., H.Y., J.W., J.E.D., I.S.C.) and Neurobiology and Behavior (Z.P., D.M.), State University of New York at Stony Brook, Stony Brook, NY; Department of Pharmacology (R.B.R.), Columbia University, College of Physicians and Surgeons, New York, NY; and Department of Biological Science (R.W., R.T.W.), University of Tulsa, Tulsa, Okla.
Correspondence to Dr Ira S. Cohen, Department of Physiology and Biophysics, 8661 SUNY, Stony Brook, NY 11794-8661. E-mail icohen{at}physiology.pnb.sunysb.edu
Abstract—HCN cation channel mRNA
expression was determined in the rabbit heart and neonatal and adult
rat ventricle using RNase protection assays. In the rabbit SA node, the
dominant HCN transcript is HCN4, representing >81% of the
total HCN message. HCN1 is also expressed, representing
>18% of the total HCN mRNA. Rabbit Purkinje fibers contained almost
equal amounts of HCN1 and HCN4 transcripts with low levels of HCN2,
whereas rabbit ventricle contained predominantly HCN2. The SA node
contained 25 times the total HCN message of Purkinje fibers and 140
times the total HCN message of ventricle. No reports of
hyperpolarization-activated current
(If) exist in rabbit Purkinje fibers,
and we could not record If in rabbit
ventricular myocytes. To investigate the possible role of
isoform switching in determining the voltage dependence of
If, we determined the prevalence of HCN
isoforms in neonatal and adult rat ventricle. We had previously
determined the threshold for activation of
If to be 
-70 mV in neonatal rat
ventricle and -113 mV in adult rat ventricle. In both neonatal and
adult rat ventricle, only HCN2 and HCN4 transcripts are present.
The ratio of HCN2 to HCN4 is 5:1 in the neonate and 13:1 in the
adult. Taken together, these results suggest that different cardiac
regions express different isoforms of the HCN family. The HCN1 and HCN4
isoforms are most closely associated with a depolarized threshold for
If activation, whereas the HCN2 isoform is
associated with a more negative activation curve. The full text of
this article is available at http://www.circresaha.org.
Key Words: RNase protection assay • mRNA distribution • hyperpolarization-activated current
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