Sensory transduction and sensory receptors Flashcards
Describe the composition of the layers in the retina and their functions:
Outermost layer = photoreceptors (rods/cones) which mediate the sense of sight
Middle retinal layer = bipolar cells which receive signals from photoreceptors and transmit these to the RGC
Innermost layer = RGC axons form the optic nerve, via which they project to the brain
Describe the chemical environment at rest in photoreceptor cells:
At rest (dark), glutamate is continuously released and stops when there is a stimulus
There is also a high [cGMP] which leads to the opening of non-specific cGMP gated ion channels
Leading to the free movement of Ca2+/Na+
Therefore DP the membrane = glutamate release
Explain why the potential sits at an intermediate level:
So the cell can respond strongly to both directions
Describe the signal transduction pathway in photoreceptor cells:
Rhodopsin in outer segment, absorbs a light photon causing a co-factor within the protein to change from the cis to trans form
Leads to a series of unstable intermediates
The last of which activates a G protein in the membrane called transducin
Transducin activates cGMP specific-PDE which hydrolyses cGMP to 5’ cGMP
Leads to decreased in intracellular [cGMP] = closing of cGMP-gated ion channels
Which leads to decrease in Na+ flow = HP as membrane becomes more negative
Due to the change in membrane potential Ca2+ influx decreases + decreased [Ca2+] due to closing of VGCC
Leads to less calcium-induced exocytosis of glutamate to bipolar cells
Glutamate excites postsynaptic bipolar and horizontal cells
Due to the decrease in glutamate one population of bipolar cells will be DP and another HP depending on receptor = metabotropic/ionotropic
Describe the termination of the signal transduction pathway in photoreceptor cells:
Hydrolysis of GTP to GDP inactivates T in a timely manner = sped up by GAPs
Low intracellular Ca2+ = dissociation of GCAP-Ca2+ leading to GCAP restoring intracellular cGMP levels, which leads to the opening of cGMP-gated ion channel allowing movement of +ve ions = restoring dark current
Low intracellular Ca2+ = dissociation of GAP-Ca2+ = deactivation of transducin
Low intracellular levels lead to dissociation of RK-recoverin-Ca2+ = RK phosphorylates metarhodopsin II which reduces its binding affinity for transducin
Arrestin deactivates metarhosopsin II = restoration of dark current
Low intracellual Ca2+ levels makes calmodulin-Ca2+ complex within cGMP-gated ion channels sensitive at low cGMP levels = restoring dark current
Enzymatic reduction of retinal to retinol
Deactivation of PDE
Phosphorylation of opsin
Describe how GAP stops the transformation of cGMP to GMP:
Interacts w/alpha subunit of transducin
Causes hydrolysis of GTP to GDP
Therefore halts the action of the PDE
Compare the control of cGMP levels by cGMP PDE and guanylate cyclase:
cGMP activity is increased by light, leading to closure of cGMP-gated ion channels and decrease in Na+ due to decreased [cGMP]
Leading to hyperpolarisation, decrease in Ca2+ influx and therefore intracellular Ca2+
GC activity is increased by decreased intracellular Ca2+
Leads to increase in [cGMP] = opening of cGMP-gated ion channels
Leading to Na+ influx and DP
Leading to Ca2+ influx and therefore increase in intracellular Ca2+
Describe the fate of all-trans retinal and arrestin:
All-trans retinal transported to pigment epithelial cells to be converted into all-trans retinol, precursor to 11-cis retinol
Removal of arrestin
Compare the adaptation abilities of rods and cones after photopic illumination:
Cones adapt very rapidly as not completely bleached after period of photopic illumination as some PP still active so can still function
Initial phase is biochemical with rapid photopigment regeneration thereafter
Rods can do far better but need around ~20 mins to reach that sensitivity, PP completely bleached after photopic illumination and inactive PP are inhibitory
Slow recovery due to slow regeneration of rhodopsin
Describe PP regeneration in cones:
All-trans retinal converted to all-trans retinol by all-trans retinol dehydrogenase
Transported to muller cells
Then converted into 11-cis retinol by all-trans retinol isomerase
Then either stored in MC as retinyl esters to transported back to cones
Where it is transformed into 11-cis retinal by 11-cis retinal dehydrogenase
Explain how the PP regeneration pathway is an explanation of dark adaptation in cones:
Presence of 11-cis retinal dehydrogenase in cones
Not present in rods, only in retinal pigment epithelium
Explain the difference in PP regeneration between cones and rods in terms of rate, supply etc:
Rate at which both use PP is similar, however regeneration much quicker in cones
Due to the much faster secondary visual cycle used by cones only, in muller cells
Slower regeneration in rods reduces amount of pigment burnt through to no purpose when rods saturated
Supply is the rate limiting step
Compare the segments of rods and cones:
Rods = long outer segments with densely packed discs, capable of capturing each photon passing along length
Cones = outer segment much shorter and contain less PP
Describe the number of rods needed for a visual effect:
5-14 rods needed to absorb each photon in retina
To produce a perceivable visual effect in humans
Compare the sensitivity of rods and cones in terms of their responses:
Rods = sensitivity boosted by prolonged response, can follow a flickering right up to ~20Hz + suffer temporal blurring
Cones = responses terminated much more quickly, can follow a flickering light up to ~70Hz at the expense of sensitivity
Compare the adaptation of rods and cones in terms of supply and responses:
Rods = Limited adaptation and restricted supply of 11-cis retinal
Responses saturate and become non-functional at light levels greater than twilight
Cones = Very efficient adaptation and a very rapid supply of 11-cis retinal
Can function without saturation over a huge range of light levels
Define critical flicker frequency (CFF) and describe what it depends on:
Lowest frequency at which a flickering light is indistinguishable from a non-flickering light of the same mean luminance
Depends on termination
What are tip links, describe their protein composition:
Extracellular filaments that connect stereocilia to each other
Or to the kinocilium in the inner hair cells of the inner ear
Made up of two cadherin molecules = protocadherin-15 and cadherin 23
Briefly describe mechanotransduction:
Where cells convert mechanical stimulus into electrochemical activity
Occurs at base of tip links which contain spring-gated cation-selective channels
Allow K+/Ca2+ to enter hair cell from the endolymph that bathes its apical end
If hair cells deflected towards kinocilium = DP
If hair cells deflected away from kinocilium = HP
Describe the fast reflux, the issue it creates and how that issue is solved:
Channels allow fast ion influx to create a rapid response - big and high permeability
However, if Na+ used then small cells will have a serious metabolic problem in pumping those ions back out
Solved by outsourcing ion pumping from stria vascularis
K+ passively corrected by K+ diffusing out via basal leak channels
So restoration of MP restores conc change as well
Describe the advantages of using a cation in fast reflux:
Extremely rapid response (endolymph potential co-varies with high frequency hearing limit)
Outsourcing metabolically demanding activity
Describe the function of myosin in terms of tip links:
Crawls along actin cytoskeleton
Controlling tip link tension
Hence sensitivity
Describe the function of Ca2+ in adaptation in tips:
Ca2+ effects both speed and extent of adaptation in tip links of stereocilia
If [Ca2+ buffer] increased in cell, then Ca2+ is more rapidly bound once it enters = slows adaptation
If cell DP, then driving force for Ca2+ influx decreases, which reduces Ca2+ entry = slowing/abolishing adaptation
Increase in Ca2+ oppposes channel opening
Compare fast and slow adaptation:
Slow - keeps tip link tension at middle of optimal working range in face of changes in structure/constant deflection
Fast - operates within timescale of the auditory response = speeding closure of channels
- Responsible for stereocilia tuning to specific frequencies at different locations on the BM
- At different locations kinetic of fast/slow appropriate to frequency response
What is a thermoreceptor:
A sensory-end organ stimulated by heat or cold
What is a nociceptor:
Neurons preferentially sensitive to noxious stimuli or stimuli that would become noxious if prolonged
Explain the term polymodal in terms of thermo-sensitive nociceptors:
Respond to a range of damaging stimuli
As they have a range of different channels and receptors in their distal endings
What are temperature sensitive afferent:
Membrane channels that change shape w/temperature
Open when temp reaches specific range
What is TRP:
Transient receptor potential family of ion channels
Many are temperature transducers
Describe the function of TRPV1 in terms of temperature response:
Change shape at 45 degrees celsius (temp at which heat = damaging)
Allowing cations to enter
Depolarising the cell
Signalling that damage is about to occur or already has
What is a KO mouse:
A knockout mouse is a lab mouse in which an existing gene has been inactivated or “KOd” by replacing it or disrupting it with an artificial piece of DNA
Describe the action of inflammatory mediators:
Increase the prob of opening and hence shift the activation curve towards lower temperatures
2 mechanisms:
- Activate PKA/PKC via a GPCR
- Activate tyrosine kinase w/growth factor receptors
Phosphorylate channels and change activation temp from 43 degrees celsius - downwards
Can shift activation below body temp (hence inflammatory pain w/out need for stimulation)
Describe the response of TRPV1 to inflammation:
Injury evokes +ve FB and the reverse of adaptation, inflammation upregulates TRV1 expression
Upon tissue damage and inflammation = inflammatory mediators released
Increase sensitivity of nociceptors to noxious stimuli = increased sensitivity to painful stimuli (hyperalgesia)
Or pain sensation in response to non-painful stimuli (allodynia)
Most sensitising mediators activated PLC pathway
Phosphorylation of TRPV1 by protein kinase C = sensitisation of TRPV1
PIP2 cleavage by PLC-beta = disinhibition of TRPV1 and increased sensitivity of TRPV1 to noxious stimuli
Describe the link between TRPV1 and neurogenic pain:
Upregulation and sensitisation of TRPV1 associated with neuropathy and if it becomes self-sustaining then may result in neurogenic pain
Describe how capsaicin is used to protect plants:
Protect from being eaten
By mimicking one of the inflammatory mediators that stimulate TRPV1
Describe 3 things that cause TRPV1 channels to open:
Temp greater than 43
Presence of inflammatory mediators or H+
When bound to botanical “warning” chemicals of the vanilloid family
Describe desensitization of TRPV1:
Upon prolonged exposure to capsaicin
- Ca2+ influx/intracellular Ca2+ mediates this
Signalling pathways such as calmodulin, calcineurin, decrease of PIP2
Overall, desensitization of TRPV1 = paradoxical analgesic effect of capsaicin
