Physiology 3140A Lecture Notes - Lecture 11: Transducin, Phosphodiesterase, Chromophore
22 May 2018
School
Department
Course
Professor
Physiology 3140
Dr. Rylett
Lecture 11
- The photon of light changes the energy state of the retinal chromophore, leading to a
conformational change in the rhodopsin GPCR to couple the transduction and then couple the
effector, phosphodiesterase
- In the dark, this activity is low bc you dont have that system coupled
- In the light, the activity of phosphodiesterase is high bc the effector is coupled into that
- Note: Ca2+ and guanylate cyclase levels are inversely related
Amplification of the signal
- Like many biological processes, you can have a single event being amplified so that the cell can
use that single event and multiply the response
- Absorption of single photon of light by single molecule of rhodopsin leads to: amplification of
the signal
- This causes the energy level of the retinal chromophore to be changed and the conformational
shape change to happen
- This doesnt coupled : with the G protein
o Its a large amplification so that single photon and rhodopsin molecule can amplify up to
about 500 G protein
o These dont couple at the same time – sequential events
- During the time that the receptor is in a diff conformation bc the photon changed the energy of
retinal, it can couple with 1 G protein transducin, this can go off to an effector, it can couple to a
second G protein→it can keep on doing this during that time frame when the receptor is
activated
- So the G protein transducin couples 1:1 with the effector
- SO, You dont get amplification at the level of the G protein and the effector but you do at the
level of the receptor and G protein
- Then the 500 phosphodiesterase molecuels that are activated can chop off 105 cGMP molecules
o So from a single photon of light 105 cGMP molecules get degraded in the cell
- This is a GRADED EFFECT
o Were only looking at a single photon of light rn
o But if you have 2 or 4 photons of light, it would be a graded effect
(within a certain range)
- The affinity for cGMP for these cation channels must be relatively low
o 105 cGMP molecules only relates to about 250 cation channels
o so you have to have a lot of cGMP to regulate the opening/gating of
the relatively fewer number of those cation channels
- the # of cations that are flowing through those cation channels is huge
o Na+ and Ca2+ concentration outside the cell is very high
o And the inside of cell is very negative compared to outside of cell
o And bc they are +ively charged, they are flowing through
- So when 250 cation channels close, 10 million cations/sec are prevented
from entering- this is HUGE
o This translates into 1 mV of the cell changing its membrane potential
- POINT IS: cGMP has to be in a relatively high concentration to open a few
cation channels – dont memorize all those numbers
find more resources at oneclass.com
find more resources at oneclass.com
Adaptation to varying light levels
- Ex: youre in a dark environment and when you go outside into bright sunlight, our eyes take a
few moments to adapt
- Eyes can sense that relatively small changes of light
- How do our eyes accomadate for the large changes in light level (dark room→bright sunlight) or
small changes in light level (cloud going over the sun)?
- cGMP are critical bc cGMP concentration in the cell determines how many cation channels are
open or closed, how much Ca2+ is coming into the cell, which is going to determine guanylate
cyclase and the amount neurotransmitter release
o the neurotransmitter release is the important part as this is what is going to determine
how much info is communicated to your visual cortex
- cGMP levels fluctuate widely,
o in the dark, high levels of cGMP, low guanylate cyclase
o in the light, guanylate cyclase levels are still low, but then it starts to increase
- Ca2+ level is what determines the guanylate cyclase activity
- Timing is very important
o As you go from dark to light, there has to be a gradient in bw
o How do we get high cGMP level when you have low guanylate cyclase
o It has to get there from the last time there was light, when there was low Ca2+ and the
guanylate cyclase level went up
How is guanylate cyclase activity regulated?
- in the dark,
o guanylate cyclase is held inactive in the retinal rod cell
o before it was dark, it was light, guanylate cyclase activity increased, created a lot of
cGMP but then you went into the dark SO we have a lots of cGMP but the Ca2+ is being
pumped out
o this is going to regulate the guanylate cyclase activity
o guanylate cyclase activity is normally held low bc it binds to another protein =
RECOVERIN
▪ similar to PKI and phosphatase inhibitor associated with PKA
o recoverin is a parallel protein process in the cell where the protein alters the function of
another rreally important protein
▪ its job is to regulate the activity of cytosolic guanylate cyclase
▪ when Ca2+ concentration is HIGH in the cell, it binds to recoverin
▪ so recoverin is a Ca2+ binding protein
▪ it senses the Ca2+ concentration in the cell, it has a calmdulin molecule
associated with it
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
The photon of light changes the energy state of the retinal chromophore, leading to a conformational change in the rhodopsin gpcr to couple the transduction and then couple the effector, phosphodiesterase. In the dark, this activity is low bc you don(cid:495)t have that system coupled. Note: ca2+ and guanylate cyclase levels are inversely related. In the light, the activity of phosphodiesterase is high bc the effector is coupled into that. Like many biological processes, you can have a single event being amplified so that the cell can use that single event and multiply the response. Absorption of single photon of light by single molecule of rhodopsin leads to: amplification of the signal shape change to happen about 500 g protein. This causes the energy level of the retinal chromophore to be changed and the conformational. This doesn(cid:495)t coupled (cid:883):(cid:883) with the g protein.
