Membrane-bound proteins that activate G proteins after binding neurotransmitters.
Primarily located along dendrites or cell body, but can be present anywhere along the neuron if there is a synapse.
Important for receiving incoming information from other neurons.
Slower but longer-lasting effects compared to ionotropic receptors.
Structure and Function
G Proteins: Composed of three subunits: alpha, beta, and gamma.
Resting state: Alpha subunit bound to GDP.
Multiple types of alpha subunits, each initiating different cellular cascades.
Neurotransmitter binds to GPCR, allowing it to interact with a specific G protein complex.
Activation leads to:
Exchange of GDP for GTP in the alpha subunit.
Separation into alpha-GTP and beta-gamma subunits.
Alteration of effector proteins’ functions, such as ion permeability or second messenger cascades.
Second Messenger Cascades
Can lead to long-term, widespread, and diverse effects like enzyme activation or gene transcription alteration.
Beta-gamma subunit:
Can open or close ion channels, e.g., in muscarinic acetylcholine receptors in the heart -> opens potassium channels (GERC channels), hyperpolarizing the cell and slowing heart rate.
Alpha subunit pathways:
Different receptors (alpha or beta-adrenergic) cause different effects depending on the coupled G protein (Gs, Gi, or Gq).
Cyclic AMP Pathway
Initiated by Gs alpha subunit; inhibited by Gi alpha subunit.
Adenyl cyclase converts ATP to cyclic AMP.
Cyclic AMP activates protein kinase A (PKA):
Phosphorylation alters protein function.
Can gate ion channels, alter permeability, modulate channel activity, or target proteins for neurotransmitter synthesis and release.
CREB transcription factor phosphorylation leads to gene transcription.
Long-lasting effects based on transcribed genes.
Phospholipase C Pathway
Initiated by Gq-alpha subunit.
Phospholipase C splits PIP2 into IP3 and DAG.
DAG interacts with protein kinase C; IP3 releases calcium from the endoplasmic reticulum.
Calcium acts as a second messenger, binding to calmodulin and activating CAMK.
PKC and CAMK phosphorylate proteins, affecting cellular functions.
Signal Amplification and Termination
Amplification: One receptor can activate multiple G proteins, leading to significant cellular effects.
Termination:
Alpha subunit converts GTP back to GDP, inactivating the G protein.
Protein phosphatases remove phosphate groups.
Mechanisms exist to remove calcium and degrade second messengers.