Lecture 5- Transduction Mechanisms

What is signal transduction?

The process by which a signal received by a receptor on the post-synaptic membrane is communicated to appropriate sites in the cell.

List five examples of cellular responses.

• Contraction,

• relaxation,

• secretion,

• growth,

• change in metabolism.

Name the four classes/types of receptors based on transduction mechanism.

• Type 1: Ligand-Gated Ion Channels (Ionotropic Receptors)

• Type 2: G-Protein Coupled Receptors (GPCRs) or Metabotropic Receptors

• Type 3: Kinase-Linked and Related Receptors

• Type 4: Nuclear Receptors or Intracellular Receptors

Describe Type 1 receptors (Ligand-Gated Ion Channels).

Activation leads to a change in ion conductance. Receptors for fast neurotransmitters (e.g., Nicotinic acetylcholine, GABAA, glutamate). The receptor is part of the ion channel protein itself, and the response is very fast (milliseconds).

Explain how Type 1 receptors work.

When an agonist binds, a conformational change opens the ion channel, allowing ions to flow down their electrochemical gradient.

Give an example of a Type 1 receptor and its action.

Acetylcholine binding to nicotinic receptors (nAChR) at the skeletal neuromuscular junction. This opens the channel, increasing Na+ and K+ conductance, leading to depolarization and muscle contraction.

Describe the structure of a typical ionotropic receptor.

Five protein subunits form a transmembrane structure with a central pore, which carries a negative charge and allows positive ions (Na+ and K+) to pass through when open.

Give another example of a Type 1 receptor and its action.

GABAA receptors, where activation by an agonist opens the Cl- channel, causing hyperpolarization.

What is the effect of Glutamate receptors?

They cause opening of channels permeable to Na+/K+/Ca2+ in the membrane and leads to fast synaptic transmission as a result of fast depolarisation.

Describe Type 2 receptors (G-Protein Coupled Receptors).

The receptor couples to a G-protein, leading to a response. This is the largest receptor family, including receptors for many hormones and slow transmitters like muscarinic acetylcholine receptors and adrenergic receptors. Responses take seconds to minutes to hours.

What is the structure of GPCRs?

GPCRs consist of a single polypeptide with an extracellular N-terminus, an intracellular C-terminus, and seven transmembrane domains.

Explain the mechanism of G-protein activation.

Coupling of the α subunit to an agonist-occupied receptor causes the bound GDP to exchange with intracellular GTP. The α-GTP complex then dissociates and interacts with a target protein. The βγ complex may also activate a target protein.

What are second messengers?

Located in the cell and can alter cell function. Examples: cyclic AMP (cAMP) and inositol triphosphate (IP3) and diacyl glycerol (DAG).

Give examples of G-protein targets.

Adenylyl cyclase (for cAMP formation) and phospholipase C (for IP3 and DAG formation).

Describe Type 3 receptors (Kinase-Linked and Related Receptors).

These receptors mainly respond to protein mediators. They feature an extracellular binding domain linked to an intracellular domain by a single transmembrane helix. The intracellular domain is often enzymic, possessing protein kinase or guanylyl cyclase activity. Examples include receptors for insulin and growth factors. Responses take minutes to hours.

Explain the mechanism of Type 3 receptors, exemplified by insulin.

Insulin binding leads to dimerization of receptors, autophosphorylation, and cellular responses like glucose uptake.

Describe Type 4 receptors (Nuclear Receptors).

Lipid-soluble ligands bind to the receptor, forming a complex. This complex then binds to DNA to regulate gene transcription. Examples include steroid hormone receptors. Full response can take hours or days.

Give an example of how a single transmitter can produce different effects.

Acetylcholine can have excitatory effects on intestinal smooth muscle via muscarinic receptors but inhibitory effects on the pacemaker tissue of the heart.