Synaptic transmission III+ sensory transduction I

Where are voltage-gated Ca2+ channels localized relative to transmitter release sites?

Near the sites of transmitter release (active zones).

the amount of transmitter release is a function of the level of ______?

presynaptic depolarization

What did the voltage-clamp experiments by Llinás (1982) prove about presynaptic depolarization?

Depolarization of the presynaptic terminal is not sufficient for release; Ca2+ entry is required.

What protein is used in imaging to reveal 'microdomains' of Ca2+ entry in the presynaptic terminal?

Aequorin

What was the result of 'caged calcium' (e.g., Nitrophen) injection experiments in the squid giant synapse?

An increase in presynaptic intracellular Ca2+ is sufficient to trigger rapid transmitter release.

Comparison: How do BAPTA and EGTA differ as Ca2+ chelators?

BAPTA is a fast Ca2+ chelator, while EGTA is a slow Ca2+ chelator.

What toxin is used to fluorescently label ACh receptors to visualize their distribution?

alpha-bungarotoxin.

What three experiments proved that calcium entry sites are located in presynaptic active zones?

1.) Fluorescence-imaging of calcium microdomains by Llinas

2.) BAPTA / EGTA injection into presynaptic terminal

3.) Fluorescently labeled calcium channels (with conotoxin, bungarotoxin, or antibodies) observed in active zones

Definition of quantal release

Release of neurotransmitters by synaptic vesicle exocytosis in discrete packets

What was the first evidence for quantal release?

MEPPs occurred at random intervals and were consistently the same size.

What are MEPPs?

tiny, spontaneous electrical fluctuations in the postsynaptic muscle membrane, even when the presynaptic motor nerve was completely at rest.

How does Curare affect EPPs and MEPPs at the neuromuscular junction?

It reduces the amplitude of both in a graded fashion by blocking nicotinic ACh receptors (nAChRs).

What is the effect of Prostigmine on evoked EPPs and spontaneous MEPPs?

It increases their amplitude and duration by inhibiting the enzyme acetylcholinesterase (AChE).

Why does bath-applied ACh cause graded depolarization but not increase MEPP frequency?

Because MEPPs are caused by discrete packets of ACh, while bath application is a continuous spread of single molecules.

What happens to stim-evoked EPPs when extracellular Ca2+ levels are significantly lowered?

The responses become very small and fluctuate in step-wise multiples of the MEPP amplitude.

Which statistical distribution was first applied by deCastillo and Katz (1954) to describe vesicular release?

The Poisson distribution

What anatomical technique did Heuser et al. (1979) use to capture vesicles in the act of fusion?

Freeze-fracture technique combined with scanning electron microscopy (EM).

Why is 4-aminopyridine (4-AP) added to synaptic preparations in quantal release studies?

It blocks K+ channels, causing spike-broadening and increasing the number of quanta released.

Heuser et al. found a 1:1 correlation between which two observed variables?

Vesicle exocytosis an quantal release.

Which experimental technique uses a carbon fiber electrode to detect catecholamine release from chromaffin cells?

Amperometry.

In the SNARE mechanism, which proteins are the v-SNARE (vesicular SNARE)?

Synaptobrevin, Synaptotagmin

Which two proteins serve as t-SNARE (target SNARE) proteins in the plasma membrane?

Syntaxin and SNAP-25.

What is the primary role of Synaptotagmin in transmitter release?

Ca++ sensor

What is the function of the regulatory protein Munc 18-1 in vesicle docking?

It holds Syntaxin in a folded, inactive configuration.

Which protein stabilizes the 'ternary SNARE complex' during the priming of vesicles?

Complexin

The 'ternary SNARE complex' consists of which three proteins?

Synaptobrevin, Syntaxin, and SNAP-25.

What event triggers vesicle fusion?

Ca++ binding to synaptotagmin

What is the function of the protein Dynamin in vesicle recycling?

It pinches off the neck of the endocytosed vesicle from the plasma membrane.

In eukaryotic cells, what is an 'endosome'?

membrane-bound compartment in eukaryotic cells.

What does clathrin binding to receptors cause?

Bending deformation of membrane and formation of “soccer-ball”-like latices around endocytosed vesicles.

Where are Ribbon Synapses located in the body?

Retinal photoreceptors, bipolar cells, and hair cells of the inner ear.

Synaptic ribbons are primarily composed of which protein?

RIBEYE protein

The specific sensory modality that most commonly activates a particular sense organ?

Adequate stimulus

The ability to detect a specific modality is referred to as a _____.

Sense

What type of ion channels are typically associated with mechanoreceptors?

Stretch-gated cation channels

Which major class of sensory cells utilizes G-protein-coupled receptors called rhodopsins?

Photoreceptors

What are 2 examples of chemoreceptors?

Taste & olfactory receptor

Menthol is known to activate which specific type of thermal receptor in the skin?

Cold receptors

In which part of the mammalian brain are warm and cold receptor neurons located for internal temperature sensing?

pre-optic/anterior hypothalamus

What is the primary function of nociceptors?

Detecting tissue-damaging (painful) stimuli

What is the function of electroreceptors?

to detect weak bioelectric fields generated by other organisms

What is the function of magnetoreceptors?

Responds to weak magnetic fields

Which light-sensitive protein found in the eyes of birds is associated with magnetoreception?

Cryptochrome

What are the two distinct types of electroreceptors found in fish?

Tuberous and ampullary

What is Sensory transduction?

The process of transforming external energy into graded receptor potential, then into a spike-frequency code(AP).

Define 'Receptor Potential'.

A graded change in membrane potential of a sensory receptor cell in response to stimulation.

What is the relationship between amplitude of the membrane potential and the intensity of the stimulation?

Proportional

Which class of sensory receptors (short or long) are specialized non-neuronal cells that produce local graded potentials but no action potentials?

Short

Which class of sensory receptors (short or long) are neurons that can conduct APs in a spike-frequency code?

Long

What class of receptors are hair cells of inner ear (vestibular and cochlear)?

Mechanoreceptors

Decreasing sensory response to a maintained stimulus is called:

Adaptation

Muscle spindles utilize Group Ia afferents for _____ responses and Group II afferents for ______ responses.

Dynamic; static

Where is the protein Piezo 1 primarily expressed?

Non-sensory tissues (e.g., lung, bladder, skin, red blood cells)

Which Piezo protein is expressed in somatosensory neurons and is responsible for tactile sensation and proprioception?

Piezo 2

In the experiments by Lowenstein and Mendelson, what happened to the Pacinian corpuscle's receptor potential when the layered capsule was removed?

It changed from rapidly adapting to slowly adapting.

According to the study by Pawson et. al, what type of receptors are Pacinian corpuscles

“mechano-chemical” receptors

What information do vestibular organs detect?

static position (tilt) & acceleration of head in space, helps with balance

What information does the cochlea detect?

Intensity & frequency of sound

Moving a hair bundle toward the _____ increases the influx of K+/Ca2+ and depolarizes the hair cell.

KinocilliumF

What connects the tips of stereocilia?

Tiplinks

Where are stretch-activated ion channels located?

Near tiplinks

Where would you move the hair bundle if you wanted to DECREASE neurotransmitter release?

away from kinocilium

What does MET stand for?

mechanoelectrical transduction channel

What are TMC1 and TMC2?

Pore forming subunits in the MET channel

How does Usher’s syndrome cause deafness?

a mutation that disrupts the tip-link protein “protocadherin 15.”

The Beethhoven (Bth) mouse mutant has a mutation in ______. How does this mutation affect channel conductance and Ca2+ permeability?

TMC1; reduces both.

The endolymph fluid bathing hair bundles has ___(high/low)K+ and _____Na+ concentrations compared to _______ bathing the

hair-cell bodies.

High, low, perilymph

What is the approximate extracellular potential of the endolymph?

+80mV

What is the total resting membrane potential of a hair cell relative to the endolymph it is bathed in?

-125mV