20110105 Lecture 4 notes.txt
From Iusmphysiology
Revision as of 02:31, 6 January 2011 by 149.166.35.72 (Talk)
- started here on 01/05/2011
- quiz is over first three lectures (not today's).
- Botox wrinkle mechanism:
- Botox only affects lines.
- The use of facial nerve sets a precedent such that we have a static state that cuases wrinkles.
- Node of Ranvier vs. voltage gated K+ channels
- The channels are only found under the myelinated areas of the axon.
- None in the node.
Learning Objectives
- Review the sensation modalities
- Understand the basic steps and mechanisms in the sensory process
- We are interested in the mechanism of function, not the anatomy
Steps in the process of sensation
- First there is a stimulus.
- Then there is activation of a receptor and stimulation of a receptor AP.
- This is a translation of siganal into AP.
- It can cause an increase in AP or decrease.
- Then there is transmission to the brain.
- Then interpretation and analyzed.
- Then response is generated.
Sensory modalities
- olfaction (smell)
- vision (sight)
- gustation (taste)
- Russians love caviar and bread
- audition (hearing)
- somesthesis (touch, temperature, body position (proprioception), and pain (nociception))
Oflaction
- Air passes through cavity onto olfactory epithelium.
- Contains many types of cells:
- Olfactory neurons / receptor cells
- Have dendrites in the mucus with receptors
- must be regnerated every 4-8 weeks
- Support cells: like glial cells
- Basal cells: differentiate into receptor (olfactorY) neurons
- Olfactory neurons / receptor cells
- Contains many types of cells:
- We can only smell water-soluble things.
- Because the olfactory neuron is a true neuron:
- we have passive spread of the AP where there is no myelination (electrotonic conduction)
- They have a voltage of -70 mv
- Once the AP reaches the axon hillock a saltatory AP is produced through the cribriform plate.
Olfactory meachanism
- There are about 400 receptors in the olfactory epithelium.
- Each neuron receives only one type of odor receptor.
What?
- The receptors are g-proteins which activate adenyly cyclase (ATP -> cAMP).
- cAMP difusses up the dendrite and reaches the cAMP-ligand gated cation channel
- Allows Na and Ca+ to pass into the dendrite.
- This opens Cl- channels such that Cl effluxes.
- This depolarization spreads electrotonically to the axon hillock.
- At the hillock, an AP is generated.
- Receptor potentials look much like APs.
Something about negative feedsback, missed it.
Olfactory bulb neuronal network
- A single neuron expresses a single
- Granular and perigranule cells are inhibitory to olfactory neurons.
- They modulate stimulation and allow for desensitization to odors.
- Up to 1000 afferent neurons converge to a glomerulus which is invervated by a single olfactory neuron.
Vision
- The retina contains the photoreceptors.
- The fovea contains more rods than cones.
- The photoreceptor signals end up in the optic nerve (CN2).
- We will focus on the fovea.
Fovea in detail
- The retina is "inverted" (?).
- The rods and cones are deep to the light, so light must travel through the many supporting cells to get to them.
- However, the distance across these supporting cells is very short: 200 micrometers.
- Because it is so small, there is no need to generate APs in the supporting cells.
- We don't need to know the layers.
- Therefore, we use simple electrotonic conduction of the AP along the dendrites.
- At the point of the ganglion cells, the dendrites converge and the AP is conducted via saltatory conduction.
- GABA
- STimulated GABA sensitive Cl- channels.
- This is important for determining which path the AP takes in bipolar cells.
- Amacrine cells:
- Role is not too clear so we won't talk about them.
- Meuller cells:
- Glial cells that support bipolar cells.
- Pigment epithelium contains important supporting cells that absorb and pass on the nutrients needed by the photoreceptors and supporting cells.
- All the cells have ribbon synapses.
- Recall that these are used so we can maintain constant stimulation.
Rod and cone anatomy
- Cones = color vision
- Rods = greyscale
- Synaptic terminal,
- inner segment:
- Contains.Nucleus and mt
- Outer layer:
- Photosensitive membranes
- Diff in rod and cone
- Cones have infolding of outer membrane to increase area of membrane to increase photon absorption.
- Rods have free floating disks from the outer segment which express rhodopsin to be given to vesicles and disks.
- We have 1:16 rods:cones.
- The fovea has predominantly cones, however.
Mechanism of phototransduction
- Our photoreceptors are still secreting NT even when asleep because they are depolarized.
- They are depolarized because the inner segment is secreting cGMP which activate cGMP-gated non-selective cation channel (Na and Ca influxing).
- Our voltage is not zero, however, because of K+ channels that move K+ outward (effluxing).
- This will generate hyperpolarization (because we are asleep and we are effluxing more K+ than influxing Na and Ca+ so the voltage is becoming more negative).
- Deem = dim. :)
Visual transduction
- The disks have opsins, a g-protein receptor (7 transmembrane domains, etc.).
- These are diff because they are bound to cis-retinal which is isomerized when it absorbs a photon.
- Cis-retinal then changes isomers to rhodopsin and we call it meta-rhodopsin because it is "activated".
- Meta-rhodopsin activates transducin, the g-protein.
- Tranducin turns on phosphodiesterase which cleaves cGMP to straight chain GMP.
- This causes a closing of the cGMP-gated cation channels.
- Guanyly-cycase is constitutively activated, so there is a constant source of cGMP, but when phosphodiesterase is activated, the levels decrease.
- The constitutive activation assures that the neurons will not become too desensitized (because there will always be basal levesl of Na and Ca influx.
- K+ channels in the outer segment cause hyperpolarization of the neuron when they allow efflux of K+ from the neuron.
- There are three types of opsins which allows us to detect three colors of light.
- Rods absorb 500nm light
- Cones express three other types of opsins that absorb: 419nm (blue), 533nm (green), 564nm (long, yellow / red).
- cis-retinal is inherently and tightly bound in the receptor (it doesn't leave to be converted back to cis from meta).
Gustation (the sensation of tasting )
- Innervated by facial (CN7), glossopharyngeal nerve (CN9).
- These innervate diferent parts of the tongue.
- Anterior = facial; posterior = glossopharyngeal.
- We have pillae that contain up to 150 tastebuds.
- Tastebuds have many cells in them:
- Taste cells (receptors)
- Transformed epithelial cells, not neuronal cells.
- Form electrical and chemical synapses.
- Not all form chemical synapses but if they dont' they will have electrical synapses with other receptor cells that do have chemical synapses
- Supporting cells
- Taste cells (receptors)
Putative mechanisms of taste transduction
- We have multiple tastes: salt, sweet, umani (aa, generally), bitter.
- Bitter is associated with toxins.
- The mechanism is different for each "taste".
- Salty comes from activity of epithelium sodium channels:
- Highly expressed in kidney, too, so we know lots about them.
- IMportant for na reabsorption and water retention.
- Has three subunits.
- Protein is constinutively active: always open, allowing Na into the taste cell to cause depolarization.
- Depolarization causes activation of voltage gated cA channels, then AP, then release of serotonin in synaptic cleft of facial nerve.
- Highly expressed in kidney, too, so we know lots about them.
- Bitter test
- detects Acids
- Protien senstivie channels
- mechanism is the same: Na permeability, Ca channels open, Ca influx, AP, release of serotonin
- Sweet and Umani and some bitter:
- Occurs through T1 / T2 (for sweet), T1 / R3 (Umani), T2 (bitter).
- These are through g-protein which activate Phosphorlipase C which cleaves PIP2 to form DAG and IP3.
- IP3 causes IP3R on the ER to release Ca+.
- DAG cuases opening of Ca+ channels on the outer membrane (TRPM5) to augment Ca influx.
- This channel has similar structure to the others we've seen.
- Influx of Ca+ causes an AP.
- All these receptors are expressed on all receptors (we think) but it isn't totally clear the distribution and differentiation mechanisms.
- Type II taste cells don't express any voltage-gated Ca channels so they may not detect...?
Hearing
- The cochlea is important for sound sensing.
- Our low is 20 kHz and high is 200 hz.
- The cochlea is importnat for low and the helic? is for high.
- There is a narrow membrane at the base but narrow at the apex (helic?).
What? Something about the two membranes being opposite...
- Place coding is the specific area of th emembrane that vibrates given the frequency of a sound wave.
- There are three important parts:
- The scalar media contains endolymnph which is rich in K+ (125 miliMolar). This causes a very high positive potential inside because marginal cells move K+ into that area. **The high levels of K+ make the potential positive for cells in scalar media.
- Didn't talk about other two areas.
Organ of corti
- There is a basalar membrane which helps determine the coding of place.
- There are two types of hair cells:
- Outer hair cells
- Insures fine tuning of inner hair cell sensitivity.
- Contain prestin which is able to contract when depolarized.
- When depolarziaed, the outer cells contract and the change of physiologicl location fine tunes the inner hair cells.
- inner hair cells
- Important for hearing sound.
- Outer hair cells
- The rate of AP in cochlea is proportional to the sound amplitude. This is called rate coding.
===Mechanotransduction in the hair cells of the inner ear===
- Hair cells have a potential of about -40 mV at rest.
- This makes sense because the tectorial membrane pushes the villi toward the hair cells and cuases opening of some channel.
- When Tectorial membrane goes up, the hair cells are caused to open K+ channels such that K+ rushes in.
- This stimulates Ca+ channels which causes the cell to release glutamate at the synapse.
- We use disks, not ribbons, for release as a mechanism of modulation.
Skin
- We have several types of mechanically sensitive structures in our skin.
- Meissner:
- Sensitive only initially to a stimulus--fast adaptation.
- Merkel's disks
- Sensitive to steady pressure.
- Slow adaptation.
- Pacinian:
- Ruffini
- slow adaptation
- stretch sensitive
- Review this table as you didn't get everything down.
- Cold receptors are fast adaptors
- Pain receptors are slow adaptors
Pacinian corpuscle
- DEG / ENac
- Demyelination is
- An axon which comes to the corpuscle is myelinated but gets myelinated inside?
This made no sense, read the slide.
- Dr. O says we should look up the rest in the book and that it is pretty clear.
- stopped here on 01/05/2011 at 12PM.