Adrenergic Regulation of HCN4 Channel Requires Protein Association with β2-Adrenergic Receptor
| Autor: | Naoto Hoshi, Seungwoo Kang, Derek L. Greene, Anastasia Kosenko |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Potassium Channels Adrenergic receptor Immunoblotting Molecular Sequence Data Cyclic Nucleotide-Gated Cation Channels Muscle Proteins Adrenergic Biology Alpha-1B adrenergic receptor Biochemistry Membrane Potentials TRPC1 Internal medicine Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Humans Protein Isoforms Myocytes Cardiac Amino Acid Sequence Receptor Molecular Biology Cells Cultured Ion channel Sinoatrial Node Sequence Homology Amino Acid Isoproterenol Cell Biology Adrenergic beta-Agonists Potassium channel Rats Cell biology HEK293 Cells Pyrimidines Endocrinology Animals Newborn Multiprotein Complexes Receptors Adrenergic beta-2 Signal transduction Peptides Ion Channel Gating Signal Transduction HeLa Cells Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 287:23690-23697 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.366955 |
| Popis: | β1- and β2-adrenergic receptors utilize different signaling mechanisms to control cardiac function. Recent studies demonstrated that β2-adrenergic receptors (β2ARs) colocalize with some ion channels that are critical for proper cardiac function. Here, we demonstrate that β2ARs form protein complexes with the pacemaker HCN4 channel, as well as with other subtypes of HCN channels. The adrenergic receptor-binding site was identified at a proximal region of the N-terminal tail of the HCN4 channel. A synthetic peptide derived from the β2AR-binding domain of the HCN4 channel disrupted interaction between HCN4 and β2AR. In addition, treatment with this peptide prevented adrenergic augmentation of pacemaker currents and spontaneous contraction rates but did not affect adrenergic regulation of voltage-gated calcium currents. These results suggest that the ion channel-receptor complex is a critical mechanism in ion channel regulation. Background: Protein complexes often play critical roles in signal transduction. Results: The HCN4 channel binds the β2-adrenergic receptor to form a macromolecular complex. Disruption of this channel-receptor complex abolishes adrenergic modulation of pacemaker currents and spontaneous contraction rates in sinoatrial nodal cells. Conclusion: The channel-receptor association is critical for cardiac chronotropic regulation. Significance: Channel-receptor complexes are the fundamental form of channel regulation. |
| Databáze: | OpenAIRE |
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