Week 5 Flashcards
Are ion channels always open?
No they can open and close in response to different signals such as voltage, chemical messengers and neurotransmitters, or heat.
What is the general resting potential of a cell?
Negative
With NA+ outside the cell and K+ inside the cell
And Cl- and Ca2+ outside the cell…
Two ions that depolarize a cell?
Na+ and Ca++
Both are in higher concentration outside a cell so when they flow into a cell the voltage goes up.
2 ions that hyperpolarize a cell?
Cl- and K+
K+ is in higher concentration inside a cell so when it flows out the cell becomes more negative
Cl- is in greater concentration outside the cell so when it flows into a cell it becomes more negative
What is hyperpolarizong a cell?
Making it more negative inside
What is depolarizing a cell?
Making it more positive inside.
Three questions to ask when figuring out which way the membrane potential is shifting?
- What ion?
- What direction is it flowing?
- What charge is it carrying?
What is in highest concentrations inside a cell?
K+
What is in high concentration outside the cell?
Na+
Ca2+
Cl-
What is hyperkalemia?
Elevated extra cellular K+
This makes the difference between outside positive charge and normal inside negative charge bigger…
Ie changes the resting potential
Depolarization of the membrane causing alterations in and even failure of action potentials to generate a response in muscles and heart
What are some permeable drugs?
Aspirin, steroid hormones, local anesthetics
How is a cell balanced?
When K+ gradient balances the force of it wanting to leave the cell versus the need for the charge to be zero.
K+ is in higher concentration in the cell and wants to leave- chemical force outward
But The inside of the cell is negative and thus attracts the positively charge K+, electrical force inward
When the two balance the cell is slightly negative and most the K+ is inside the cell.
What happens in depolarization?
The cell becomes more positive
What happens in hyperpolarization?
The cell becomes more negative
What happens when Na+ channels open?
Depolarization
More positive in cell
What happens when K+ channels open?
Hyper polarized more negative inside and positive outside
What happens when non-selective cation channels open?
Will equilibrate based on balance of charges of Na+ and K+ going in and outside
What happens when K+ channels close?
Depolarization more positive in cell
What happens when Cl- channels close?
Depolarization more positive in the cellular cycle
How do anesthetics work?
They disrupt the action potential signals signals
Such as locals that block Na+ channels, puffer toxins also block them
Lidocaine makes Na channels inactive
True of false
Action potentials are either on or off and depend on a threshold and once they reach the threshold the shape is the same.
True
How fast can action potentials propagate?
Up to 100 meters a second
Can a higher injected current create a stronger response ie more action potentials once the threshold is reached?
Yes a stronger current can generate multiple action potentials in series
How does an action potential work on Na channels? Ie order of operations
Depolarization
Na+ channel opens
Na+ enters the cell
Which in turn triggers more depolarization and more Na channels opening and more Na+ entering
This is a positive feedback loop
What is the Hodgkins cycle?
The positive feedback loop of Na+ channels
How to K+ channels respond to a depolarizing stimulus?
Depolarization ie positive charge
Opens K+ channels and charge flows out bringing cell back to negative.
This repolararizes cell and brings it back to negative charge and channels shut
What is threshold and how is it triggered?
When enough of a signal/voltage change causes enough channels to open to trigger the positive feedback loop which continues till all the channels have opened
How is a cell depolarizer after and action potential ie how does the voltage return to resting state?
Na+ channels switch to an inactive and closed state where they can’t be triggered again in the depolarizing state of the cell
They only reset when when returns to resting value
And K+ channels open more slowly than Na channels so they allow charge to resets in cell by leaking positive charge out of cell
How do action potentials propagate down an axon?
As a wave of depolarization
The leading edge provides the initial depolarization to open Na+ channels that cause each new section to reach threshold just before the next section
Two factors that control speed in action potential propagation in non-myelinated axons?
- Axon diameter
2. How much current or charge is needed to depolarize the membrane
How can speed of an action potential be sped up?
By wrapping the nerve in myelin which block Na+ channels
This makes it so that areas in myelin don’t depolarize and the potential travels from one node of Ranvier where Na+ channels are to another….
K+ channels can form in Myelin
How mush does myelin speed up an action potential?
Can be more than 100x faster
Where is myelin made?
Typically glial cells
In the Peripheral nervous system- Schwann cells
In the central nervous system- oligodendrocytes
What is myotonia congenita?
When Cl- can’t move into cell to repolararize causing sustained discharge of action potentials
Fainting goats too
How do most general anesthetics work?
By altering synaptic functions
What is a synapse?
Junction between two neurons or and neuron and the end like a muscle or sensors
2 types of synapses and where are they commonly found?
- Electrical- sense systems ie retina, liver and cardiac muscle
- Chemical- brain, neuromuscular inervations
How do electric synapses work?
Bidirectional connexon pores that connect the cytoplasm of two cells that allows current to pass through
What are electrical synapses effective for?
Synchronization groups of cells such as the heart
Many cardiac disease stem from a disruption in heart muscle nerve gap junctions
Steps of a chemical synapse action potential propagation in motor neuron ? (5 of them, others work similar)
- Action potential depolarizes the nerve side of terminal
- Depolarization causes voltage gated Ca2+ channels open and Ca2+ enters the nerve cell
- Ca2+ triggers vesicles filled with ACh to fuse with nerve cell wall and dump ACh into junction/cleft
- ACh diffuses across cleft and binds to ACh receptors which open non selective cation channels in the muscle cell which depolarizes the muscle cell (end plate potential) and leads to action potential in muscle aka muscle twitch
- ACh is removed from the cleft by enzyme degradation (ACh-esterase)
Under normal conditions does triggering the end plate potential lead to reaching the threshold in the muscle and propagation of a muscles action potential?
Yes it does but disease can disrupt that
What is Myasthenia gravis?
A disease that manifest as muscle weakness where muscle action potentials fail to propagate in muscles
How is a motor neuron action potential turned off?
ACh-esterase degrading ACh in the synaptic cleft
What does botulinum toxin do?
Disrupts proteins (cleaves protein involved in fusion/snare proteins) involved in ACh release into the cleft and nerves don’t cause a muscle to contract and causes paralysis
What does latrotoxin (black widow spiders) do?
Dumps ACh into synaptic cleft causing uncontrolled muscle contractions
What does bungarotoxin (cobras) do?
Binds ACh receptors so they can’t receive the signal and muscles won’t contract
Name 3 toxins he pointed out that disrupt the neuromuscular junction?
Botulinum, latrotoxin black widows, bungarotoxin cobras
Names some other neurotransmitters other than ACh that work in other synapses?
Glutamate
GABA
Glycine
How are other neuro transmitters removed from the cleft?
Transporters and diffusion
Name a difference that other transmitters have from neuromuscular end-plate potentials in terms of size?
They are often smaller
Two features that chemical transmitters share?
- Chemical transmitter is stored in vesicles
2. And increase in Ca2+ triggers the fusion of vesicles and release of neurotransmitter
How do paralytic agents used in surgery work?
Suppressing the ACh signal but binding to but not activating the ACh receptors in the synaptic cleft
Competitive inhibition
Factors that cause diversity in chemical synaptic transmission?
Type of transmitter
Difference in receptors
How multiple inputs are combine or integrated by post synaptic cell
Are synaptic transmissions at muscles alway unidirectional?
Yes they trigger contractions only
Are synaptic transmission always depolarizing?
No they be both hyper (inhibitory/IPSP) and depolarizing (excitatory/EPSPs)
What channels are triggered by hyperpolarization (inhibitory/IPSP)?
K+ and Cl- channels
What channels are triggered by depolarizing (excitatory/EPSPs)?
Mostly no specific cation channels that are dominated by Na +
What ions are used in general junctions and what are used in neuromuscular junctions?
General- Na+, K+, Cl-
Neuromuscular- Ca2+
What are the two types of receptors that mediate speed of response fast and slow?
Ionotropic- fast the receptors is the channel
Metabotropic- slow it is G-protein coupled receptor which causes a cascade response
Name some inhibitory chemical messengers and where they commonly are?
GABA- CNS
Glycine- spinal cord
K+ or Cl- selective channels
Name some excitatory chemical messengers?
AMPA/ Kainate and NMDA which are glutamate in the CNS
Nicotinic ACh
No. Selective cation channels
Explain the reflex pathway?
- Afferent neuron receives signal which is sent to spinal cord
- There the signal is split into two.
A. Excitatory (epsp) signal along efferent neuron to extensor muscle using glutamate and non selective cation channels- net inward currentB. Inhibitory (IPSP) signal to flexor muscle using glycine and K+ or Cl- selective ion channels
What is the speed difference between ionotropic and metabotropic receptors?
~1000x in both latency and duration
msec vs sec
Name 5 ways drugs target neuron signaling and some examples?
- Receptor enhancement- benzodiazepines enhance GABA receptors (IPSP)
- Receptor Agonists- LSD binds to sera Tobin receptors and turns them on
- Receptor antagonists- strychnine block glycine receptors remember glycine is often and IPSP signal in reflex’s
Haloperidol blocks and binds to dopamine receptors so there is no dopamine response - Block enzymatic degradation- Eserine inhibits ACh breakdown at neuromuscular junctions so contractions happen longer
- Reuptake blockers- SSRIs keep natural serotonin around longer
Two general anesthetics and what they do?
Ketamine- NMDA (glutamate g-protein receptor) receptor antagonist that decrease EPSP signaling
Halothane- GABA/glycine receptors agonists that increases inhibitory signals
How do many pain reducing agents and opioids work?
Target GPCRs like opioid receptors to either block or activate to inhibit signaling
Example activation can open K+ channels which is an inhibitory signal
3 common features of sense receptors ?
- Physical stimulus at one end where signal is then sent along nerve line
- Receptor activation either opens or closes ion channels to convert it to an electrical signal and receptor potential is graded and thus can increase in strength based on stimulus strength
- Some cause action potentials some cause voltage changes that go to a the synaptic terminal where they can release neurotransmitters
Name 4 different types of nerve endings?
- Free nerve ending often pain receptors
- Encapsulated nerve endings often pressure such as vibration or stretch
- Specialized sense cell such as taste or vision
- Specialized sense cell that has axons that extend back to CNS- aka all one cell such as olfactory receptor
If two different stimuli tickle the same receptor do they elicit the same response? Examples?
Yes once the signal is converted to a voltage signal it is essentially the same signal
Example both fire and spicy can travel along the same nerve fiber and feel the same
Or cold/hot/chemical can activate the same receptor
Or cochlear implant can do the same thing
What type of receptors do olfactory cells use and where is the information processed?
GPCRs- there are over a 1000 different types that are highly specialized to bind to very specific molecule and can even differentiate between different stereoisomers
Processed in the olfactory bulb organized by receptor types/glomerulus
This accounts for diversity of odor perception
How does a concussion affect the sense of smell?
It can sever the olfactory nerves. They can take a longtime to repair
How are speed differences is sense accounted for?
Myelinated or not and different receptors ie GPCR metabotropic or ionotropic
Which two taste sense are ionotropic and which are metabotropic?
Salty and sour/acid are ionotropic
Umami, bitter and sweet are GPCRs aka metabotropic
What are nociceptors?
Pain receptors and they are found in every tissue of the body except brain.
Classified by type response
Do all nociceptors respond to only one type of stimulus?
No some are polymodal such as heat and spicy or cold and pain
What is the difference in speed between a sharp localized pain and diffused more full pain?
Sharp is fast along myelinated nerves versus slow unmyelinated for dull longer diffused pain
Names some braid categories or nociceptors?
Non noxious mechanical
Noxious mechanical
Thermal
Chemical
Thermal and chemical are often polymodal
Mechanical are often polymodal for different types of mechanical stimulus
Location of action of general amnesic anesthetics?
Paralytic action of general anesthetics?
Local anesthetics?
Amnesic- brain
Paralytic- spinal cord
Local- at receptors/ stop AP generation
