Lesson 21 - How cells change phenotypes_2025

Page 1: Overview

• Lesson 21: Our senses and minds with GPCR

• Key Topics: Caffeine, Adenosine

• Date: March 10, 2025

Page 2: Learning Objectives

G-protein Signaling in the Retina

• Rapid Signal Transmission: G-protein signaling at the retina allows the eye to rapidly respond to light.

• Adaptation to Light: The eye adjusts to dim and bright light conditions to maintain optimal vision.

Nitric Oxide as a Signaling Molecule

• Function: Nitric oxide (NO) triggers relaxation of smooth muscle cells, impacting blood flow.

Effects of Brain Stimulants

• Neuronal Circuitry: Different stimulants affect neuronal circuitry, primarily affecting dopamine levels.

• Cholera Toxin: A classic example illustrating how toxins can disrupt signaling pathways.

Page 3: Olfactory GPCRs

Distinguishing Smell

1. Olfactory GPCR Receptors:

   • Affiliated with multiple odorant molecules.

   • Individual neurons have varied GPCR repertoires leading to unique smell signatures.

   • Odorant receptors are located on cilia of olfactory neurons in the nasal cavity.

2. Olfactory Neuronal Signaling:

   • Activation: GPCR activates G-alpha, stimulating adenylyl cyclase (AC), resulting in cAMP production.

   • Depolarization: cAMP opens Na+ channels, triggering action potentials.

Page 4: Vision and GPCRs

Photoreceptors in Vision

1. Types of Cells:

   • Cone Cells: Detect RGB colors.

   • Rod Cells: Sensitive to light intensity.

2. Rod Cell Functionality:

   • In darkness: Stable firing via cGMP-gated Na+ channels, releasing neurotransmitters to optic nerves.

   • Light exposure: Inhibition of firing occurs due to changes in membrane potential.

Signal Transduction

• GPCR activates transducin (G-alpha), leading to cGMP phosphodiesterase activation which decreases cGMP levels, closing Na+ channels and inhibiting synaptic neurotransmitter release.

Page 5: Speed and Sensitivity of Vision

1. Speed:

   • Image recognition occurs in about 13 milliseconds, processing roughly 75 images per second.

2. Sensitivity:

   • A single photon can cause a 1 mV shift in membrane potential.

   • Amplification occurs through multiple stages allowing significant adaptation to varying light intensities.

   • Example of response dynamics: From 1 to 10 photons producing outputs from 1 mV to 10 mV.

Page 6: Taste Sensation

Taste Bud Functionality

1. Chemical Response:

   • Taste buds release serotonin when exposed to chemicals.

2. Taste Types:

   • Basic Tastes: Sweet, salty (Na+), sour (H+), bitter.

     • Gated Channels: Salt, Sour, Bitter mediated via electrical signals.

     • GPCR: Bitter (diverse), Sugar, Amino acids processed through Ca++ waves.

Page 7: GPCR and the Senses

iClicker Question

• Which sense does NOT use GPCR signaling?

  • Options: A. Smell, B. Vision, C. Tastes, D. Sound, E. All use GPCR

Page 8: Rod Photoreceptors

Light Sensitivity and Drugs

• Rod cells utilize GPCRs in their light-sensing mechanism which influences cyclic GMP phosphodiesterase action and light response.

• Effects of drugs on rod cells will vary on their action type, altering the light-sensing capacity.

Page 9: Signaling Mechanisms and Control

Blood Vessel Dilation

1. Control Mechanism:

   • Acetylcholine (Ach) interacts with GPCR, leading to calcium ion release which activates nitric oxide synthase.

   • NO diffuses, binds to guanylyl cyclase in muscle cells, promoting relaxation via cGMP.

2. Drugs Impacting Blood Pressure:

   • Examples: Nitroglycerin, Viagra (inhibit cGMP phosphodiesterase).

3. Paracrine Signaling:

   • Important for coordination among cell types in tissues/organs.

Page 10: Smooth Muscle Relaxation

iClicker Question

• Which situation could lead to smooth muscle relaxation independent of acetylcholine?

  • Various options involving defects in guanylyl cyclase and other pathways.

Page 11: Substances Affecting GPCR Signaling

Brain Stimulants

1. Adderall/Cocaine:

   • Related to dopamine levels affecting attention and neuronal firing.

   • Inhibit reuptake of dopamine, enhancing synaptic activity.

2. Cholera Toxin:

   • Modifies G-alpha, preventing GTPase activity, causing excessive cAMP and chloride ion channel activity leading to diarrhea.

3. Caffeine:

   • Competes with adenosine GPCRs, reducing sleep-promoting effects, influencing dopamine activity.