G protein-coupled receptor signaling pathway involved in heart process

Definition

Target type: biologicalprocess

An G protein-coupled receptor signaling pathway which contributes to a circulatory system process carried out by the heart. [GOC:BHF, GOC:mtg_cardiac_conduct_nov11, PMID:17376402]

G protein-coupled receptor (GPCR) signaling pathways play a crucial role in regulating heart function, impacting processes like heart rate, contractility, and blood pressure. These pathways involve a series of intricate interactions between receptors, G proteins, and downstream effectors, leading to a cascade of intracellular signaling events.

1. **Ligand Binding and Receptor Activation:** The pathway initiates when a specific ligand, such as hormones, neurotransmitters, or other signaling molecules, binds to a GPCR on the surface of heart cells (cardiomyocytes). This binding event triggers a conformational change in the receptor, activating its intracellular domain.

2. **G Protein Activation:** Activated GPCRs interact with heterotrimeric G proteins, which consist of alpha (α), beta (β), and gamma (γ) subunits. The activated receptor catalyzes the exchange of GDP for GTP on the α subunit, leading to its dissociation from the βγ dimer.

3. **Signal Transduction:** The activated α subunit, carrying the bound GTP, interacts with downstream effector proteins, which are responsible for generating specific intracellular signaling events. These effectors can include:
- **Adenylate cyclase:** This enzyme catalyzes the production of cyclic AMP (cAMP), a second messenger that activates protein kinase A (PKA). PKA phosphorylates various proteins involved in cardiac function, such as ion channels, contractile proteins, and regulatory enzymes.
- **Phospholipase C:** This enzyme hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3). DAG activates protein kinase C (PKC), while IP3 triggers the release of calcium ions from intracellular stores, increasing intracellular calcium levels.

4. **Calcium Signaling:** Calcium ions play a pivotal role in cardiac muscle contraction. Increased intracellular calcium levels, triggered by GPCR signaling, bind to troponin C, initiating a cascade of events that lead to muscle contraction.

5. **Regulation of Cardiac Function:** The downstream signaling events initiated by GPCR activation regulate various aspects of heart function, including:
- **Heart Rate:** GPCRs can increase or decrease heart rate by modulating the activity of ion channels involved in pacemaker activity.
- **Contractility:** GPCRs can influence the strength of heart muscle contractions by altering the intracellular calcium levels and the sensitivity of contractile proteins to calcium.
- **Blood Pressure:** GPCRs contribute to the regulation of blood pressure by influencing vascular tone and blood volume.

6. **Signal Termination:** To ensure proper regulation and prevent overstimulation, GPCR signaling pathways need to be terminated. This occurs through several mechanisms, including:
- **Ligand Dissociation:** Ligands eventually dissociate from their receptors, reducing receptor activation.
- **GTP Hydrolysis:** The α subunit of the G protein possesses intrinsic GTPase activity, hydrolyzing GTP to GDP, returning the G protein to its inactive state.
- **Desensitization:** Prolonged activation of GPCRs can lead to receptor desensitization, where the receptors become less responsive to further stimulation.

In summary, GPCR signaling pathways play a vital role in the regulation of heart function, influencing heart rate, contractility, and blood pressure. These pathways involve a series of complex interactions between receptors, G proteins, and downstream effectors, leading to a cascade of intracellular signaling events that ultimately modulate cardiac activity.'
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