COGS 107A - FINAL STUDY

What ions flow through the ligand gated receptors at a synapse to generate an excitatory postsynaptic potential (EPSP)?

Na+ ions flow into the cell, causing depolarization and making the postsynaptic neuron more likely to fire an action potential.

when an EPSP is evoked, what membrane potential is the cell trying to reach?

reversal potential

signaling mechanisms for modulate behaviors are: …

…metabotropic

reversal potential

the membrane voltage when there is no net current—Na+ and K+ ions drive the membrane voltage toward a specific value, reflecting the electrochemical equilibrium for those ions.

signaling mechanisms to mediate simple reflex behaviors are…

…ionotropic

signaling mechanisms that begin slowly and persist for long periods of time are…

…metabotropic

signaling mechanisms for an ion channel is part of the receptor macromolecule is…

…ionotropic

signaling mechanisms that are second messengers are…

…metabotropic

signaling mechanisms where changes can be local and spread by activating proteins and enzymes are…

…metabotropic

signaling mechanisms that directly open ion channels are…

…ionotropic

T/F both AEA and 2AG are structurally very similar and metabolize to arachidonic acid

True. they are 2 primary endocannabinoids.

T/F Inhibition of vgCa+ channels, activation of potassium channels, and direct interference w synaptic vesicle release mechanisms are all associated w cannabinoid transmitter release disruption.

True. endocannabinoids act retrogradedly—from post to presynaptic—they suppress the classical neurotransmitters

T/F conductance is the inverse of resistance. therefore, as conductance increase, resistance decreases

True. conductance (G) is the reciprocal of resistance (R) —> G = 1/R

if the intracellular and extracellular concentration of ION-A are equal, ION-A is the only ion in the neuron, and the neuron is only permeable to ION-A, what is ION-A's equilibrium potential?

0mV bc there is no driving force—gradient is the same inside and outside

calculate the rate of change of voltage (V/s) w the given values:

injected current pulse = 80nA

patch area = 0.0003 cm^2

specific membrane capacitance = 10^-5 (F/cm^2)

dV/dt = I/C —> 26.7mV

what underlies the depolarizing ramp and the threshold voltage at the beginning of an action potential

the depolarizing ramp is the charging of the membrane by the pulse of the inward current (more positive, more Na+ ions; sodium influx through the voltage-gated sodium channels initiate rapid depolarization aka increasing positive charge in the cell)

electrical gap junctions are ______

…signals using direct ionic current through connexons.

electrical gap junctions are used for ______

…the synchronization of populations of neurons.

chemical synapses are ____ and use ____ to signal

slow; neurotransmitters

chemical synapses are ______

the most common type of synapse in the CNS

At the end of an axon (and its collaterals) the tips are button-shaped cytoplasmic enlargments called what?

terminal boutons

gray’s type i synaptic membrane structures

excitatory, asymmetrical ; have higher postsynaptic density

gray’s type ii synaptic membrane structures

inhibitory; symmetrical; postsynaptic density = presynaptic density

____ receptors contain ion channels which are directly opened when a ligand attached to the binding site

• ligand-gated

• neurotransmitter-gated (same as ^^)

• ionotropic

T/F otto loewi demonstrated that the vagus nerve released a chemical transmitter—he shoed this by proving that the second frogs heart contraction force increased in the presence of the first frog’s heart solution

false: the second heart’s rate decreased in the rate of contraction

t/f IPSP can be produced when K+ leaves the post-synaptic cell

True: when K+ leaves the cell, it makes it more negative, causing hyperpolarization —> less likely for AP to fire

T/F metabotropic receptors are linked to g-proteins which when activated, can open ion channels

True. Metabotropic receptors are linked to G-proteins, which can open (or close) ion channels when activated. They open GIRK (K+) channels where K+ leaves the cell, causing hyperpolarization.

what is situ hybridization?

A method of localizing specific mRNA transcripts for proteins in tissue

• shows you WHERE a gene is expressed

what is necessary for synthesizing a neurotransmitter?

pre-cursor materials, co-factors, and enzymes

To synthesize a xtransmitter…

enzymes need to be in an active form

To synthesize a xtransmitter needs…

localization to the appropriate compartment

Is an ion a chemical compound that binds to a specific site in a receptor ?

No, those are ligands—once a ligand binds, the door opens that allow the ions in or out

Muscarine is a(n) _____ for mAChR

Agonist

• it binds to and activates mAChRs.

• It mimics the effects of acetylcholine at muscarinic receptors.

bathing an axon in TTX is ______ in ______

more effective; reducing the AP than procaine

The receptor found at the neuromuscular junction is the ______

nicotinic acetylcholine receptor (nAChR)

the neurotransmitter that binds to nAChR is _____

ACh that binds onto skeletal muscle

TTX blocks _____

…voltage-gated Na+ channels.

TEA blocks _____…

…voltage-gated K+ channels.

• delayed repolarization

absolute refractory period

… is the brief time during and immediately after an action potential when a neuron cannot fire another action potential no matter how strong the stimulus is.

• needs time to reload

why does the absolute refractory period happen?

It occurs because the voltage-gated Na⁺ channels are inactivated.

when does the absolute refractory period happen?

during most of repolarization (makes cell more negative)

Na⁺ channels →

…deal w depolarization

K+ channels →

…deal w repolarization

Ca²⁺ channels →

…deal w neurotransmitter release

The ligand is usually a ________.

neurotransmitter—chemical messenger

GPCR activation is overall:

Ligand binds → receptor changes shape → G-protein activates → second messengers → cell response

GPCR interacts with ______

…a heterotrimeric G-protein (α, β, γ subunits).

When activated GPCR causes _________…

…GDP → GTP exchange on Gα —> Gα separates from βγ

Unlike most neurotransmitters, endocannabinoids:

• are not stored in vesicles

• are made on demand

• travel backward across the synapse—retrograde synapse

Axoplasmic transport

…is the microtubule-based system that uses kinesin and dynein to move cellular cargo between the soma and axon terminal in neurons.

Neuronal cytoskeleton

…is a coordinated system of

• microtubules (transport)

• actin (synaptic remodeling)

• neurofilaments (structural support)

• it maintains neuron shape, enables cargo movement, and supports synaptic plasticity—disruption of this system, especially tau-related microtubule failure, contributes to diseases like Alzheimer’s.

Driving force = Vm - Eion

• direction of ion flow

• how strong the flow is

K⁺ at rest =

small outward current

Na⁺ at rest =

 strong inward current, positive charge when Na+ moves into cell (makes cell less negative)

What two forces drive the equilibrium potential?

electrical force (charge attraction/repulsion) and diffusion (ion movement down concentration gradient)

What is Electrical Conductance? What are the Units?

Electrical conductance, g, is a material property that describes how easy it is for charged particles to move (“conduct”) through the material. The units of conductance are Siemens (S).

why is electrical conductance important for neuronal signaling?

The signaling is done through the movement of ions (charged particles) into and out of neurons - if neurons had zero conductance, they couldn’t signal.

What is Electrical Resistance?

Electrical resistance, R, is a material property that describes how hard it is (or how much “resistance” there is to) moving charged particles through a material. The units of resistance are Ohms (Ω).

How is electrical resistance related to conductance?

• Resistance is related to conductance in that it is the inverse of conductance, given by the equation R = 1/g. 

• 0 conductance is equivalent to infinite resistance, and 0 resistance is equivalent to infinite conductance.

What is Ohm's Law? Provide two different ways to express the equation (in terms of conductance and resistance)

An equation that describes the relationship between voltage (V), current (I), and resistance (R) in an electric circuit or analogous system.

What is the equilibrium potential?

The equilibrium potential is the electrical potential difference across a neuron membrane that balances the forces created by the electric and chemical gradients, stopping net movement of ions across a selectively permeable membrane.

How does the equilibrium potential relate to the Nernst equation?

The Nernst equation calculates the equilibrium potential for a single permeable ion.

How would you express the ionic driving force?

The ionic driving force is the force created on ions due to the voltage difference between a neuron’s actual membrane potential and the ion’s equilibrium potential.

Who is Otto Loewi?

pharmacologist who demonstrated chemical synaptic transmission via frog heart experiments

• demonstrated that chemical transmission exists

Who were Furshpan and Potter?

physiologists who proved electrical synapses exist in their experiments

• demonstrated that both electrical and chemical synapses mediate motor neuron-muscle signaling

What are 4 essential differences between chemical and electrical synapses?

1. Electrical synapses use gap junctions (instantaneous) while chemical synapses use the synaptic cleft (slower)

2. Electrical synapses can involve a secondary messenger while Chemical synapses do not

3. Electrical synapses transmit bidirectionally while Chemical synapses are unidirectional

4. Electrical synapses can transfer subthreshold potentials while Chemical synapses produce excitatory or inhibitory synaptic potentials (EPSP/IPSP)

What are the 10 steps of chemical synaptic transmission?

1. Transmitter synthesis/storage in vesicles

2. Action potential reaches presynaptic terminal

3. Depolarization opens vg-Ca Channels

4. Ca influxes into the terminal

5. Ca triggers vesicle fusion with presynaptic membrane

6. Transmitter exocytosis into the synaptic cleft

7. Transmitter binds to post-synaptic receptors

8. Post-synaptic channels open/close

9. Post-synaptic potential (EPSP/IPSP) alters excitability

10. Vesicle membrane retrieval

How would you approach thinking about the notch?

describes a local minimum amplitude in the sodium currents during the recording of an action potential

 voltage-gate ion channels…

…open/close in response to changes in membrane potential while ligand-gated channels require a neurotransmitter binding to the channel in order to open.

 voltage-gate ion channels are…

…selectively permeable to specific ions while ligand-gated channels may allow multiple ions to pass through.

Ligand-gated channels…

…produce excitatory/inhibitory post-synaptic potentials (EPSPs/IPSPs) depending on the neurotransmitter type.

Ligand-gated channels exhibit…

amplification properties where multiple channels are activated by a single neurotransmitter.

Small-molecule neurotransmitters are:

• Stored and released from synaptic vesicles

• Mediate rapid synaptic actions

• Synthesized at the axon terminal

Neuropeptides are:

• Stored and released from secretory granules

• Modulates slower, persistent synaptic functions

• Synthesized in the Soma or cell body

What is a graded potential?

A membrane potential that changes as a function of location such that there is one “peak” location with highest voltage, and the magnitude of the voltage decreases in proportion to the distance from the peak location.

 spatial summation

multiple signals come in from different locations at the same time and are then summed

 temporal summation

multiple signals come in at different times from the same location before being summed

 spatial and temporal summation

…involve multiple incoming signals combining to raise the receiving membrane’s voltage higher than it would raise from only a single incoming signal, as if the effects of the individual signals on the voltage were added (summed) together.

What does Tau tell you?

is the “time constant” for an exponential function, or a physical process described by an exponential function.

• how quickly the value of the exponential function changes in time.

• Tau is the time after which the exponential function will have changed (either increased or decreased) by a factor of 1 - 1/e =~ 0.632 =

• ~ 63% of it’s maximum change.

What does Lambda tell you?

is the “space (or length) constant” for an exponential function of space,

• how quickly the value changes as the position changes.

• the distance after which the exponential function will have changed (either increased or decreased) by a factor of 1 - 1/e =~ 0.632 =

• ~ 63% of it’s maximum change.

how is acetylcholine (ACh) and glutamate synthesized in the presynaptic terminal?

its synthesized by ChAT (choline acetyltransferase) from Choline and AcCoA (Acetyl-CoA or acetyl coenzyme A)

Glutamate…

…is synthesized by Glutaminase from Glutamine.

GABA_A + GABA_C

are ionotropic receptors and control chloride ion channels

GABA_B

is a metabotropic receptors (2nd messengers)

•  controls potassium and calcium ion channels

____ is the precursor for ____ amine xmtrs.

Tyrosine; Dopamine, Norepinephrine, and Epinephrine

Tyrosine hydroxylase…

… is present in all cells producing catacholamines.

Mediating a response (ionotropic receptors)

they directly open ion channels, allowing for rapid changes in membrane potential and _____ quick, simple behaviors (e.g., reflexes)

Modulating a response (metabotropic receptors)

they engage biochemical signaling pathways (e.g., G-protein coupled receptors) to produce persistent changes in neuronal connectivity and circuit output, _____ behavior.

 Where does the transmitter bind to the receptor in GPCR activation?

•  The primary messenger (e.g., hormone, neurotransmitter, drug) binds to the 7-transmembrane helix receptor on the membrane.

What is the heterotrimeric domain?

The arrangement of α, β, and γ subunits in G proteins, which are involved in cellular signal transmission.

Referencing mAChR, why is the GIRK called an inward rectifying potassium channel?

has high conductance for potassium when below the resting membrane potential, resulting in an inward current that returns the membrane to the equilibrium potential (rectifying)

G-protein-gated inward rectifying potassium channel (GIRK)

an inward current that returns the membrane to the equilibrium potential

receptor diversification (biogenic amines)

Different receptors for a single neurotransmitter (e.g., 7 families of serotonergic receptors, 5 dopaminergic receptor subtypes, 2 norepinephrine receptor families).

Ligand diversification (endocannabinoid system)

Multiple ligands (e.g., 2AG and AEA) can bind to the same receptor (e.g., CB1 or CB2).

classical neurotransmitters

use anterograde signaling (presynaptic to postsynaptic)

•  pre-synthesized and stored in vesicles

• composed of amino acids, amines and peptides

endocannabinoids

use retrograde signaling (postsynaptic to presynaptic)

• synthesized on demand as lipids and cannot be stored

• are lipids—can cross the lipid bilayer like nothing