Coordination of membrane excitability through a GIRK1 signaling complex in the atria
| Autor: | Tatyana T. Ivanova-Nikolova, Emil N. Nikolov |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cell signaling
Patch-Clamp Techniques Potassium Channels G protein Biology Biochemistry Heart Rate Animals G protein-coupled inwardly-rectifying potassium channel Heart Atria Potassium Channels Inwardly Rectifying Protein kinase A Molecular Biology Protein kinase C Ion channel Protein Kinase C Acetylcholine receptor Receptor Muscarinic M2 Cell Membrane Receptor for activated C kinase 1 Cell Biology Atrial Function Cell biology Rats G Protein-Coupled Inwardly-Rectifying Potassium Channels Ion Channel Gating Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 279(22) |
| ISSN: | 0021-9258 |
| Popis: | Control of heart rate is a complex process that integrates the function of multiple G protein-coupled receptors and ion channels. Among them, the G protein-regulated inwardly rectifying K+ (GIRK or KACh) channels of sinoatrial node and atria play a major role in beat-to-beat regulation of the heart rate. The atrial KACh channels are heterotetrameric proteins that consist of two pore-forming subunits, GIRK1 and GIRK4. Following m2-muscarinic acetylcholine receptor (M2R) stimulation, KACh channel activation is conferred by the direct binding of G protein betagamma subunits (Gbetagamma) to the channel. Here we show that atrial KACh channels are assembled in a signaling complex with Gbetagamma, G protein-coupled receptor kinase, cyclic adenosine monophosphate-dependent protein kinase, two protein phosphatases, PP1 and PP2A, receptor for activated C kinase 1, and actin. This complex would enable the KACh channels to rapidly integrate beta-adrenergic and M2R signaling in the membrane, and it provides insight into general principles governing spatial integration of different transduction pathways. Furthermore, the same complex might recruit protein kinase C (PKC) to the KACh channel following alpha-adrenergic receptor stimulation. Our electro-physiological recordings from single atrial KACh channels revealed a potent inhibition of Gbetagamma-induced channel activity by PKC, thus validating the physiological significance of the observed complex as interconnecting site where signaling molecules congregate to execute a coordinated control of membrane excitability. |
| Databáze: | OpenAIRE |
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