Lecture 10: Neurotransmitters and their receptors Flashcards
Chemical synaptic transmission
- NT release (+ NT R)
- ONE type (specific) of chemical communication between cells in the nervous system
Other ways of chemical communication between cells (transmitting factors): release of hormones, neurotransmitter, growth factors
NT Receptors - Categories:
Ligand-gated ion channels (ionotropic receptors): ligands regulate ion flux
directly changing the membrane potential.
G protein-coupled receptors (GPCRs; metabotropic receptors): require 2nd messenger for physiological response via intracellular signaling cascade (not all GPCRs are metabolic receptors)
which NT does not follow the cell impermeant signalling pathway (release via vesicle fusion)?
nitric oxide
Intracellular signal transduction:
Amplification of chemical signaling via activation of metabotropic NT R within the target cell
receptor -> effector molecule -> response
Heterotrimeric G proteins
(GTP-binding Proteins (G-Proteins))
α subunit or βγ subunit complex modify activity of an effector protein (different, 3 subunits of alpha, beta and gamma)
Monomeric G proteins
(a.k.a small GTPases) activated by GEF bound to receptor (e.g. Ras)
explain pic
This diagram shows how GPCRs activate G proteins to regulate cellular effectors. When an agonist binds to the GPCR, it activates the G protein, causing the α subunit to exchange GDP for GTP and separate from the βγ complex. The α-GTP and βγ subunits then activate different effectors, such as adenylate cyclase (AC), phospholipase C-β (PLC-β), ion channels (GIRK, VGCC), etc. The signal ends when GTP is hydrolyzed to GDP, allowing the G protein subunits to reassociate and reset the system.
explain
his diagram illustrates the activation of G-protein-coupled inwardly rectifying potassium (GIRK) channels via muscarinic acetylcholine receptors (mAChRs) and Gβγ subunits.
Key Steps in the Process:
Acetylcholine (ACh) Binds to mAChR
The muscarinic acetylcholine receptor (mAChR), a metabotropic receptor, is activated by ACh.
G Protein Activation
The heterotrimeric G protein (Gαβγ) is activated.
Gα exchanges GDP for GTP, causing the βγ subunit to dissociate.
Gβγ Activates GIRK Channels
The βγ subunit binds to the GIRK channel, opening it.
Potassium (K⁺) ions flow out, leading to membrane hyperpolarization, which reduces neuronal excitability.
This pathway is important in regulating heart rate and neuronal inhibition, as seen in the parasympathetic nervous system (e.g., vagus nerve slowing the heart).
Effector pathways associated with metabotropic Rs and Gα Subunit Types
Different metabotropic receptors for the same NT can also have different effects in the target cell based on the Gα-subunit. Alpha subunits depend on G protein
Second Messenger: Ca2+
sources, intracellular targets, removal mechanisms
Sources: (plasma membrane: voltage gated Ca2+ channels, various ligand gated channels), (ER: IP3 receptor, Ryanodine receptors)
Intracellular Targets: calmodulin, protein kinases, protein phosphatases, ion channels, synaptotagmins, many other Ca2+ binding proteins
Removal mechanisms: (plasma membrane: Na+/Ca2+ exchanger, Ca2+ pump), (ER: Ca2+ pump), Mitochondria
Effector pathways associated with different 2nd
messengers
Effector pathways associated with G-protein- coupled receptors - Gα Subunit Example
cAMP can act in diff ways on diff. Channels, diversifying effects on same cell
Neuronal GPCRs
One NT via different metabotropic Rs can activate different G prots – and thus be excitatory or inhibitory
A given NT can have post-and pre- synaptic effects
Identity of receptor decides the final binding/response - response of NT(in pre and post) varies based on receptor
Long-Lasting Responses Involve Changes in Nuclear Signaling
PKA , MAPK (ras), CaMKIV can phosphorylate CREB.
Involved in long-term plasticity and learning
Changes expression/shape of the protein in nucleus
Signalling cascades result in changes of gene expression, some of these changes could have long lasting effects (resulting in gene expression changes)
