Lecture 9 & 10

Lecture 8: Chemical Messengers Cont.

Signal Transduction Mechanisms

• Response mediated by membrane-bound receptors

  • Chemical Class. Types:

    • Lipophobic messengers cannot cross the plasma membrane; receptors with binding sites face extracellular fluid.

    • Receptor Categories on Plasma Membrane: 3 Types

      • Channel-linked receptors

      • Enzyme-linked receptors

      • G protein-linked receptors (GPCRs)

1. Channel-linked Receptors

• Messenger (Ligand)-gated Channels: 2 Types

  • Fast ligand-gated channels: Receptor and channel are the same protein.

  • Slow ligand-gated channels: Receptor and channel are separate proteins and coupled with a 3rd protein (G protein).

• Ion Permeability: Within cells is determined by presence of generally specific ion channels.

2. Enzyme-linked Receptors

• The receptor and enzyme are the same protein.

• Binding at receptor activates enzyme, with the receptor binding site facing interstitial fluid and enzyme's active site facing the cytosol.

3. G Protein-linked (Coupled) Receptors (GPCRs)

• Over 1000 types of GPCRs in the human body.

• Respond to signaling molecules and environmental changes.

• Activated G proteins (α, β, & γ) on the intracellular side of the plasma membrane act as links between receptor and other plasma membrane proteins.

• Effectors could be ion channels or enzymes.

Activation Process

• GPCR undergoes a conformational change as the messenger binds.

• αβγ subunit dissociates, exchanging GDP for GTP, governing target proteins.

• After hydrolysis of GTP to GDP and disappearance of the messenger ligand, subunits return to the receptor protein.

G Protein-linked Receptors: Example (cAMP)

• Effector enzymes catalyze production of second messengers.

• Example: Cyclic adenosine monophosphate (cAMP)

  • When messenger (e.g., epinephrine) activates G protein-linked receptors, αGTP dissociates and activates adenylate cyclase, converting ATP to cAMP.

  • cAMP influences heart rate, dilates blood vessels, and breaks down glycogen.

Signal Amplification by Second Messengers

• 1 messenger binds to 1 receptor leading to significant product amplification:

  • 1 messenger -> Several G proteins activated (10)

  • Each activated G protein activates adenylate cyclase generating hundreds of cAMP (5000)

  • Each cAMP activates a protein kinase A, leading to the activation of millions of proteins (2,500,000).

Membrane Potential

• Overall difference in electrical charge (mV) between the inside and outside of a cell membrane involves anions (-) and cations (+) like Na+, K+, Cl-, and Ca2+.

• Factors affecting membrane potential include:

  1. Permeability properties of the plasma membrane.

  2. Nondiffusible negatively charged molecules inside ( DNA, ATP, Cl-).

  3. Action of Na+/K+ pumps.

Equilibrium Potential

• Every ion has an Equilibrium Potential (Ex) where there's no net movement of ions across a cell membrane, expressed in mV.

• Calculation using the Nernst Equation:Ex = (61mV/z) (log [Xo]/[Xi])

  • Ex = equilibrium potential for ion x

  • Xo = concentration of ion outside the cell

  • Xi = concentration of ion inside the cell

  • z = valence of the ion.

Types of Electrical Signals: Graded Potentials vs. Action Potentials

• Graded Potentials

  • Small local changes in membrane polarity; occur in dendrites and cell body, mainly ligand-gated channels.

  • Size relative to stimulus strength and decreases with distance.

  • Can be excitatory (depolarizations) or inhibitory (hyperpolarizations).

• Action Potentials:

  • All-or-none principle; a suprathreshold stimulus triggers an action potential without altering its size.

  • Three distinct phases due to Na+ and K+ gradients:

    • Depolarization: Rapid increase in Na+ permeability leads to a spike from -70 mV to +30 mV.

    • Repolarization: Sodium permeability decreases while potassium permeability increases, returning to a negative membrane potential.

    • Hyperpolarization: Increased K+ permeability leads to membrane potential going below -70 mV.

Refractory Period

• Absolute Refractory Period: A brief period where no action potential can occur in that region.

• Relative Refractory Period: A second action potential can occur if a stronger-than-usual stimulus is applied.

Summary of Neuron Function

• The organization of the nervous system includes functional and structural divisions, with an understanding of the parts and functions of neurons and neuroglia.

• The ionic basis of action potential and the differences between graded potentials and action potentials, including the summation and conduction mechanisms, are essential for their roles in neuronal signaling.

• Effects of demyelination on conduction velocity and the relationship between potassium levels and electrical activity are also critical for understanding neuronal function.