Lesson 16: Cell Signaling Overview and Gated Channels

Signal Transduction

• Is the process of translating information from outside of the cell into a specific & limited cellular response.

• Receptor ligand binds causing a confirmational change to active state, ligand releases and returns receptor to inactive form.

Typical Signal Transduction Cascade

1. First messenger (signal)

2. Receptor protein interaction

3. Upstream signaling proteins

4. Second messengers

   1. Relays info from ligand receptor complex

5. Downstream signaling proteins

6. Target proteins (cause a response)

First Messengers include…

• Hormones

• Ions

• Small molecules

• Metabolites

• Gases

Second Messengers

• Are molecules required by most signaling pathways

• A point for amplification

• Multiple 2nd messengers produced by one signal can give multiple responses

Protein kinase activity is central to many BLANK pathways

• Signaling

• Common method for amplifying the original signal

• Can occur at any point in the pathway or multiple times

• Generates diverse responses from one signal by phosphorylating multiple target proteins

Gated ion channels

• Have a “gate” regulated by a biological signal

• Eversion: Have both open and closed conformations

• When gate is open, ions diffuse thorugh channel in direction dictated by electrochemical gradient.

Gated ion channels can be gated by:

• Physical stimuli (mechanosensitive)

• ligand binding

• voltage (membrane potential)

• pH

Voltage-gated membrane channels change conformation in response to BLANK across the membrane.

Voltage

• Voltage-gated ion channels have positively charged voltage sensors. When the inside of the cell becomes more positive, the sensors move outward due to the change in electrical forces, causing the channel to open.

  
  

Membrane potential results from…

the unequal distribution of charges across a cell.

Nernst Equation:

Δψ = V_Eq = (RT/ZF) ln ([ion]_out / [ion]_in)

• Δψ → potential across membrane, ΔV

• Use when membrane permeable to a single ion

At room temp (20°C), the equation for equilibrium potential for a single monovalent cation (Z=1) is:

V_Eq = 58 mV log ([ion]_out / [ion]_in)

Name the subunits and what they do/form in voltage-gated channels

• Each subunit has 6 transmembrane helices with an intracellular N-terminus

• Helices 5 and 6 form the channel

• Helix 4 is the voltage sensor

The intracellular N-terminus of the K⁺ channel forms an BLANK

inactivation domain

• The ball and chain model…

Ball-and-chain model

• Depolarization opens the channel → ions begin moving through it → positive charge on amino acids (the ball) move into the channel & plugs channel (keeps it open for a short time)

• How quickly the ball plugs the channel is based off of chain length

  • Shorter chain = quicker inactivation

Most neurons have the same parts, which are?

• Dendrite

• Cell Body

• Axon

Dendrites

They receive information from other neurons

The cell body (in neurons)

It contains the nucleus and most cell organelles

Axon

• Conducts action potentials away from the cell body

• Signal travels down axon

Axon terminals

They synapse with a target cell

Nerve impulses are propagated by changes in BLANK

membrane potential

Action potential

Its the rapid temporary change in membranes potential due to opening of ion channels

3 phases of action potential and what happens in each?

1. Depolarization - membrane potential becomes less negative and moves toward a positive charge

2. Repolarization - membrane potential changes back to negative charge

3. Hyperpolarization - membrane potential slightly more negative than the resting potential (also called the undershoot)

Action Potential cascade - starting at resting potential

1. membrane potential -60 mV

2. depolarization of membrane to approx -40 mV

3. opening of Na channels

4. membrane potential of +30 mV

5. closing of Na channels

6. opening of K channels

7. membrane potential -75 mV

Action potenitals propagate rapidly along the length of axons, causing what?

electrical signaling as charge spreads down the membrane

• Lots of positive charge at one spot gets attracted further down, so that charge moves down the axon

• Where positive charge used to be, it resents itself because of potassium channels, so it has no movement backwards because of falling charge

  • this forces membrane potential all the way down the axon

Ligand-gated ion channels change conformation upon BLANK

ligand binding

• can happen extracellularly or intracellularly

• Ligand itself is not transported across membrane, only opens channel

3 classes of ligand-gated channels

• Cys-loop

• Glutamate (P pore-loop)

• ATP-gated P2X channels

Cys-loop channels

• consist of 5 subunits arranged around a pore (pentamer)

  • 2 α-subunits

  • 1 β-subunit

  • 1 δ-subunit (delta)

  • 1 γ-subunit (gamma)

• Each subunit has has 3 domains

  • Extracellular (ligand binding)

  • Transmembrane

  • Intracellular (involved in opening and closing of the channel)

Acetylcholine Nicotinic Receptor

• Is a Cys-loop channel

• M2 helicies face the interior which make up the channel

• acetylcholine binds to alpha subunit & causes confirmational change so Leu unblocks channel

Nicotinic Receptors transmit neuronal signals from BLANK cells to BLANK cells

nerve

muscle

Acetylcholine (ACh)

• is a neurotransmitter synthesized from choline and acetlyCoA

• Its released from vesicles in pre-synaptic neuron

• Binding of it opens channel to Na and K ions

Acetylcholine is synthesized in, stored in, and released from BLANK

cholinergic neurons → those that respond to acytylcholine

Acetylcholine is released into the BLANK in response to an influx of Ca²⁺

synapse

Events in the transmission of nerve impulses in synapses

• release of acetylcholine from the synaptic vesible into the synaptic cleft

• increse of acetylcholine concentration in the synaptic cleft from ~10 nM to 500 nM

• Binding of acetylcholine to the ACh receptor

• increse in postsynaptic membrane permeability to Na⁺ and K⁺

• depolarization of post-synaptic membrane

Muscles contract when…

they receive signals from motor neurons

Acetylcholinesterase

• breaks down acetylcholine in the synapse cleft

  • Choline is transported back into the pre-synaptic cell to be used for ACh synthesis

Neuromuscular blocking agents (NMBAs)

• are nicotinic receptor antagonists used in conjunction with anesthesia

• Induces paralysis

  • Used for mechanical ventilation and traceal intubation

  • Used to relax muscles during surgery

• No effet on the level of consiousness or ability to preceive pain

Nondepolarizing Agents

• Competitive antagonist

• Bind to the acetylcholine receptor but do not open the channel

  • Prevent depolarization of the muscle cell → inhibits muscle contraction

• Effects of this can be reversed with acetylcholinesterase inhibitors