Physiology 3140A Lecture Notes - Lecture 22: Calcium Atpase, Rod Cell, Guanylyl Cyclase
2 May 2018
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Cell Physiology Lecture 22
Regulation of cGMP Phosphodiesterase: Role of cGMP in Signal Transduction in the
Visual System
- Retinal rod cell where cGMP and cytosolic guanylate cyclase play a key role in regulating our ability
to transduce light photons into signals that we can use as information
Anatomy of Retinal Rod Cell
- Outer segment - photoreceptive apparatus
o Receives photons of light and initiates transduction of information
o Contains: optical disks + apparatus needed to detect photons of light and
transduce information from photons of light to activate responses in the visual
system of the brain
- Inner segment - many mitochondria
o Energy factor
o Ion flow (Na, K, Ca) back and forth across the plasma membrane of the retinal
rod cell can change the membrane potential of the retinal rod cells
▪ The retinal rod cell has to be able to change its membrane potential
• Become depolarized, repolarized, hyperpolarized etc.
▪ Must be able to move up & down scale of membrane potential
▪ The cell needs a lot of metabolic energy to do that due to the proteins
that accomplish it:
• Sodium potassium ATPase – pump K+ and Na+ across the PM to
rectify the membrane potential
• Calcium ATPase
• Therefore, a lot of ATP is going to be used
o There are lot of calcium ATPase pumps and sodium potassium ATPase pumps
- Nuclear region; Has a nucleus
- Synaptic region - makes synaptic contact with nerve cells of the retina (and along the way to the
visual cortex)
o Modified form of neuron or nerve cell
o Releases neurotransmitters
▪ Note; the neurotransmitters that are released in a calcium dependent fashion
▪ If cytosolic calcium concentration goes up in the cell, it induces release of the
neurotransmitter
• Resting calcium levels in the cell cell induced to have a change in
cytosolic calcium calcium dependent phenomena in cell takes place e.g.
release of neurotransmitters
▪ Neurotransmitter release is calcium dependent event
o Neurotransmitters released are inhibitory
▪ Changes the polarity of the cell & decrease the firing pattern
o Most nerve cells have a tonic firing pattern; input from retinal rod cells & gets more of the
inhibitory neurotransmitter released. The inhibitory neurotransmitter binds to surface
receptor & lead to hyperpolarization (changing polarization of cell) making it harder to
depolarize to get an action potential from the cell. The tonic firing rate of the cell goes down
o MORE RELEASE OF INHIBITORY NEUROTRANSMITTER = LESS INFORMATION GETS SENT
TO THE BRAIN
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Responses to Light and Dark Conditions
- In the dark:
o Rod cell is strongly depolarized
o Cation (Na+ and Ca++) voltage gated Ca++ channels open
▪ A lot of sodium and calcium are moving into the retinal rod cells
▪ Membrane potential is depolarized
o Cytosolic Ca++ level high with steady released of transmitter
▪ Get a high rate of transmitter release (inhibitory transmitter)
▪ NOT SENDING ANY INFORMATION TO NEXT NEURON IN LINE, AND NONE TO THE
VISUAL CORTEX (due to the neurotransmitter being inhibitory)
o Rhodopsin is INACTIVE
o No photons hitting rhodopsin = cation channels open and gated = cations (Na, Ca) move
down electrochemical gradient (positive negative, high low)= retinal rod cell
depolarized relative to resting potential = cytosolic calcium increases (higher relative to
resting)
- Light causes:
o Cation channels to close
o Cell hyperpolarizes
▪ Na/K ATPase in inner segment work to re-establish resting levels (Na+ out, K+ in)
o Decreased Ca++ influx and decreased release of transmitter
▪ Ca pumped out by ATPase + channels closed (Ca not going back in)
o Photons of light hit the rhodopsin & it becomes activated through the conformational change
of the retinal chromophore sodium + calcium channels begin closing
o Retina rod cell can send information to the next neuron
- Na+ channels in the image are actually BOTH sodium and calcium channels = selective cation
channels
- Rhodopsin is the GPCR that is going to detect the photons of light
o Portion of the receptor analogous to ligand binding site, is an adapted form of vitamin A
(retinal)
▪ The retinal chromophore can detect photons of light
▪ When photons of light hit the retinal rod cells, it changes the energy state of the
retinal = analogous to a hormone binding to ligand site on GPCR
▪ Photon analogous to ligand
-
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Summary
DARK
LIGHT
Membrane potential
Depolarized
Hyperpolarized
Cation channels
Open
Closed
Transmitter release
Increased release
Decreased release
Cytosolic calcium
Higher level
Lower level
Transmitter inhibits postsynaptic neurons
- Illumination frees neurons from inhibition and thus excites them
o Light frees the next nerve cells that the rod cells synapses on in order to communicate
o Taking away inhibitory input to the next nerve cell
o It frees the next neuron to allow it to increase its tonic firing right – equivalent to having an
excitation
- Rate of transmitter release from rod cells is graded to light intensity
o The more light you get = more effect it has
o We are capable of detecting differences in light over a broad range. For this to happen, our
visual system at this level (level of retinal rod cells – where photons are detected) has to be
able to respond to a wide range
o Few photons of light – get few rhodopsin receptors activated
o More photons of light – get more receptors activated
▪ Note: this plays out in the amount of neurotransmitter that is released
o Whole system is synced to the number of photons of light that activate the retinal rod cells
Rod cells contain visual pigment rhodopsin
- Rhodopsin has a light absorbing portion of complex retinal (vitamin A):
o Absorption of light causes conformational change in retinal and cascade of events involving
cGMP
▪ Coupled to G protein and effector
▪ Effector = cGMP dependent phosphodiesterase
• Starts to brings in cGMP
o This is only light –dependent step in vision
- Rhodopsin is the portion of the retinal rod cell that detects light through the chromophore, retinal
(form of vitamin A) that absorbs the photon of light
- Light is absorbed by the chromophore (retinal – portion of the GPCR, rhodopsin) couples G
protein coupling effector (phosphodiesterase) that brings in cGMP
- Note; this is a graded effect
- For example: have a defect where you are deficient in retinal (vitamin A)
o The visual system does not have the chromophore associated with rhodopsin
o Would not be able to detect light
o Would not be able to detect differences in light
o ONLY LIGHT DEPENDENT STEP*
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Document Summary
Regulation of cgmp phosphodiesterase: role of cgmp in signal transduction in the. Retinal rod cell where cgmp and cytosolic guanylate cyclase play a key role in regulating our ability to transduce light photons into signals that we can use as information. Inner segment - many mitochondria: energy factor. The inhibitory neurotransmitter binds to surface receptor & lead to hyperpolarization (changing polarization of cell) making it harder to depolarize to get an action potential from the cell. The tonic firing rate of the cell goes down: more release of inhibitory neurotransmitter = less information gets sent. Na+ channels in the image are actually both sodium and calcium channels = selective cation channels. Illumination frees neurons from inhibition and thus excites them excitation. Rhodopsin has a light absorbing portion of complex retinal (vitamin a): absorption of light causes conformational change in retinal and cascade of events involving cgmp, coupled to g protein and effector, effector = cgmp dependent phosphodiesterase.
