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Functional heteromerization of HCN1 and HCN2 pacemaker channels.
J Biol Chem. 2001 Mar 02; 276(9):6069-72.JB

Abstract

An important step toward understanding the molecular basis of the functional diversity of pacemaker currents in spontaneously active cells has been the identification of a gene family encoding hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective (HCN) channels. Three of the four gene products that have been expressed so far give rise to pacemaker channels with distinct activation kinetics and are differentially distributed among the brain, with considerable overlap between some isoforms. This raises the possibility that HCN channels may coassemble to form heteromeric channels in some areas, similar to other K(+) channels. In this study, we have provided evidence for functional heteromerization of HCN1 and HCN2 channels using a concatenated cDNA construct encoding two connected subunits. We have observed that heteromeric channels activate several-fold faster than HCN2 and only a little slower than HCN1. Furthermore, the voltage dependence of activation is more similar to HCN2, whereas the cAMP sensitivity is intermediate between HCN1 and HCN2. This phenotype shows marked similarity to the current arising from coexpressed HCN1 and HCN2 subunits in oocytes and the native pacemaker current in CA1 pyramidal neurons. We suggest that heteromerization may increase the functional diversity beyond the levels expected from the number of HCN channel genes and their differential distribution.

Authors+Show Affiliations

Laboratory of Toxicology, University of Leuven, Van Evenstraat 4, 3000 Leuven, Belgium.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11133998

Citation

Ulens, C, and J Tytgat. "Functional Heteromerization of HCN1 and HCN2 Pacemaker Channels." The Journal of Biological Chemistry, vol. 276, no. 9, 2001, pp. 6069-72.
Ulens C, Tytgat J. Functional heteromerization of HCN1 and HCN2 pacemaker channels. J Biol Chem. 2001;276(9):6069-72.
Ulens, C., & Tytgat, J. (2001). Functional heteromerization of HCN1 and HCN2 pacemaker channels. The Journal of Biological Chemistry, 276(9), 6069-72.
Ulens C, Tytgat J. Functional Heteromerization of HCN1 and HCN2 Pacemaker Channels. J Biol Chem. 2001 Mar 2;276(9):6069-72. PubMed PMID: 11133998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional heteromerization of HCN1 and HCN2 pacemaker channels. AU - Ulens,C, AU - Tytgat,J, Y1 - 2000/12/27/ PY - 2001/1/3/pubmed PY - 2001/4/6/medline PY - 2001/1/3/entrez SP - 6069 EP - 72 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 9 N2 - An important step toward understanding the molecular basis of the functional diversity of pacemaker currents in spontaneously active cells has been the identification of a gene family encoding hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective (HCN) channels. Three of the four gene products that have been expressed so far give rise to pacemaker channels with distinct activation kinetics and are differentially distributed among the brain, with considerable overlap between some isoforms. This raises the possibility that HCN channels may coassemble to form heteromeric channels in some areas, similar to other K(+) channels. In this study, we have provided evidence for functional heteromerization of HCN1 and HCN2 channels using a concatenated cDNA construct encoding two connected subunits. We have observed that heteromeric channels activate several-fold faster than HCN2 and only a little slower than HCN1. Furthermore, the voltage dependence of activation is more similar to HCN2, whereas the cAMP sensitivity is intermediate between HCN1 and HCN2. This phenotype shows marked similarity to the current arising from coexpressed HCN1 and HCN2 subunits in oocytes and the native pacemaker current in CA1 pyramidal neurons. We suggest that heteromerization may increase the functional diversity beyond the levels expected from the number of HCN channel genes and their differential distribution. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11133998/Functional_heteromerization_of_HCN1_and_HCN2_pacemaker_channels_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)34606-X DB - PRIME DP - Unbound Medicine ER -