Synapses - Action Potential and Drug Targets Flashcards
What’s the resting membrane potential and what is it useful for?
– 70 mV ( is the charge difference across the membrane) one way the neurons communicate without using ATP
Resting state ion concentration (Na, K)
Na concentration high outside the membrane, K – high inside
Who sets the concentration?
Sodium potassium pump
What happens when a ligand/neurotransmitter binds to a receptor at the dendrite spine -
The membrane becomes depolarized or hyper polarized
How does excitatory action potential form?
Excitatory neurotransmitters open positively charged channels and depolarize the membrane
How does inhibitory action potential form?
Inhibitory neurotransmitters (Cl, K) are negative ions that hyper polarize the membrane
who makes the decision to propagate Action Potential or not?
the hillock by temporal or spatial summation
( The action potential is all or none)
What happens when threshold is reached?
Action potential
What happens at rising phase of Action Potential?
Na is rushing in
What happens when Na reaches its equilibrium?
Na channels become inactivated
What’s the difference between Inactive vs closed channels?
Inactive means can’t depolarize anymore, cannot respond to other/more stimulation =refractory phase = the flushing of toilet model
What’s the next step in the AP after depolarization?
the Na channels close
What’s next? After the Na channels close
Next the K channels open and remain open for a longer period causing the overshoot - the K leaves creating hyper-polarization,
What’s next? after hyperpolarization
At this point the Na K pumps use ATP to equalize the charge across the membrane
What needs to happen at the pre-synaptic membrane before releasing the neurotransmitters?
the voltage gated Ca channels need to open
What does increase in Ca concentration cause?
Readily releasable pool is emptied by the increase in Ca concentration- vesicles fuse with the membrane and empty
What are transporter proteins important for?
getting the neurotransmitter into vesicles = neurotransmitter storage
Types of Synapses (2)
Chemical and electrical
Characteristics of Chemical Synapses
- Chemical synapses are unidirectional
- Rapid, prolonged stimulation /firing can activate the reserve pool
Electrical synapses characteristics (6)
- Prevalent in hippocampus and other limbic structures
- The speed is faster because the membranes are touching (the connexons form the tight junctions)
- The origin or the type of the signal matches the response of the signal (either depolarization or hyperpolarization)
- Bidirectional (if you have multiple neurons in a row = synchronous firing)
- There is no signal renewal or salutatory conduction and over time and space the signal will weaken because of membrane resistance
- Drugs that affect membrane dynamic will have a stronger effect because the membranes are close to each other
Places where synapses can be targeted by drugs (8)
NT release (Ca channels)
NT reuptake (clear a signal from the synapse)
NT degradation – (clear a signal from the synapse by enzymatic activity)
NT synthesis
NT storage – transporter proteins
Membranes
Postsynaptic receptors
Presynaptic auto-receptors (mobilize the reserve pool by prolonged stimulation)
How can we change the strength of the synapse?
Up-regulating the number of receptors by repeated stimulation
Strength of synapses can be increased with long term potentiation which is the foundation of learning and memory ( up-regulation of receptors) (neurons that fire together, wire together)
How else can we change the strength of synapse?
Down regulation of receptors = depression of activity/less activity or response to stimulation
Long term depression underlines addictions
What happens with neurons whose connections are not supported or stimulated?
die
What is the role of microglia?
Glia have a supportive role (astrocytes that release a small amount of NT) are the ones that support new formed connection
Can we grow new neurons?
Yes
- In the dentate gyrus of the hippocampus and,
- The olfactory bulb
There are stem cells that when stimulated could form new neurons here
What can adults do to stimulate neuro-genesis?
Read Use non dominant hand Exercise Solve puzzles Use your brain
What is important when designing a Drug for the neurologic system?
Getting it to the target tissue / organ; Need to pass the BBB
What is the BBB?
A highly selective permeability barrier that separates the brain from the circulatory system and protects the central nervous system (CNS) from potentially harmful chemicals while regulating transport of essential molecules and maintaining a stable environment. - BBB is formed by highly specialized endothelial cells that line brain capillaries and transduce signals from the vascular system and from the brain
What are tight junctions?
Tight junctions = series of cross linked proteins that hold things close together, hold peripheral membrane proteins (found at the surface of the membrane) together with the actin cytoskeleton to form the ocludent family of proteins
4 Ways of trespassing the BBB
Hyperosmotic solution
Microcatheterization
Micro Bubbles
Trojan Horse
which substance easily get through the BBB?
Non-polar (lipids) through simple diffusion
How do glucose and amino acids get through BBB?
Through facilitated diffusion –active transport
Other pharmacological consideration when designing a drug
The risk of getting cleaned out once in the brain is also important
Name the cells of the nervous system and their functions
Neurons (transmission cells)
NeuroGlia (support cells)
~Astrocytes: in CNS; provides structure and support. Have “feet” that make contact with the blood vessels
~Microglia: small, mobile, Like phagocytes (engulf and consume foreign microorganisms and damaged or dead neurons)
~Oligodendrocytes: in CSN; forms myelin in CNS, like CNS version of schawnn cells
~Ependymal cells: in CNS: These cells are involved in the creation and secretion of cerebrospinal fluid (CSF) and beat their cilia to help circulate the CSF and make up the blood-CSF barrier.
~Satellite cells: in PNF; small cells that surround neurons in sensory, sympathetic, and parasympathetic ganglia.[22] These cells help regulate the external chemical environment. kind of like astrocytes but in PNF
~Schwann Cells: in PNF; forms myelin in PNS, like PNF version of Oligodendrocytes
(sorry, didn’t realize these were covered in next deck)
Where are ligand-gated channels commonly found and some examples of which ions pass through them.
We mostly talked about them on post-synaptic neuron.
Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter
Where are voltage gated channels usually found?
Often found in neurons, especially in the axon (I think).
Examples include:
~the sodium and potassium voltage-gated channels of nerve and muscle.
~the voltage-gated calcium channels that play a role in neurotransmitter release in pre-synaptic nerve endings.
G and F Table 28-3
Anatomic site of damage: Frontal Lobe
How does damage affect Memory Finding? (4)
Lateralized deficit in working memory
~Right spatial defects
~left verbal defects
~impaired recall with spared recognition
G and F Table 28-3
Anatomic site of damage: Frontal Lobe
How does damage affect Other Neurological and Medical Findings? (4 - 7)
~Personality change
~Perservation
~Chorea, dystonia
~Bradykinesia, tremor, rigidity
G and F Table 28-3
Anatomic site of damage: Basal Forebrain
How does damage affect Memory Finding?
Declarative memory defiict
G and F Table 28-3
Anatomic site of damage: Basal Forebrain
How does damage affect Other Neurological and Medical Findings?
none listed
G and F Table 28-3
Anatomic site of damage: Ventromedial Cortex
How does damage affect Memory Finding? (1)
Frontal lobe-type declarative memory deficit
G and F Table 28-3
Anatomic site of damage: Ventromedial Cortex
How does damage affect Other Neurological and Medical Findings? (1)
Upper visual field defects
G and F Table 28-3
Anatomic site of damage: Hippocampus and parahippocampal cortex
How does damage affect Memory Findings? (4)
~Bilateral lesions yield global amnesia
~Unilateral lesions show lateralizations of deficit
~Left: verbal deficit
~Right: spacial deficit
G and F Table 28-3
Anatomic site of damage: Hippocampus and parahippocampal cortex
How does damage affect Other Neurological and Medical Findings? (4)
~myoclonus
~depressed level of consciousness
~cortical blindness
~automations
G and F Table 28-3
Anatomic site of damage: Fornix
How does damage affect Memory Findings? (1)
~Global Amnesia
G and F Table 28-3
Anatomic site of damage: Fornix
How does damage affect Other Neurological and Medical Findings?
none listed
G and F Table 28-3
Anatomic site of damage: Mammillary Bodies
How does damage affect Memory Findings? (1)
~Declarative memory deficit
G and F Table 28-3
Anatomic site of damage: Mammillary Bodies
How does damage affect Other Neurological and Medical Findings? (4)
~Confabulation,
~Ataxia
~nystagmus
~signs of alcohol withdrawal
G and F Table 28-3
Anatomic site of damage: Dorsal and medial dorsal nucleus (of thalamus)
How does damage affect Memory Findings? (1)
~Declarative memory deficit
G and F Table 28-3
Anatomic site of damage: Dorsal and medial dorsal nucleus (of thalamus)
How does damage affect Other Neurological and Medical Findings? (1)
~Confabulation
G and F Table 28-3
Anatomic site of damage: Anterior Thalamus
How does damage affect Memory Findings? (1)
Declarative memory deficit
G and F Table 28-3
Anatomic site of damage: Anterior Thalamus
How does damage affect Other Neurological and Medical Findings?
none listed
G and F Table 28-3
Anatomic site of damage: Lateral temporal cortex
How does damage affect Memory Findings? (1)
Deficit in autobiographical memory
G and F Table 28-3
Anatomic site of damage: Lateral temporal cortex
How does damage affect Other Neurological and Medical Findings?
none listed
G and F Table 28-3
What are the 9 Anatomic Sites of Damage?
- Frontal Lobe
- Basal Forebrain
- Ventromedial Cortex
- Hippocampus and parahippocampal cortex
- Fornix
- Mammillary Bodies
- Dorsal and Medial dorsal nucleus (of thalamus)
- Anterior thalamus
- Lateral temporal cortex
G and F Table 28-3
What five Anatomic Sites of Damage have declarative memory deficit as a Memory Finding?
- Basal forebrain
- Vntromedial cortex (frontal lobe-type declarative memory deficit)
- Mammillary Bodies
- Dorsal and medial dorsal nucleus (of thalamus)
- Anterior Thalamus
G and F Table 28-3
What two Anatomic Sites of Damage had Confabulation as an Other Neurological and Medical Finding?
- Mammillary Bodies (also included atxia, nystagmus, signs of alcohol withdrawal)
- Dorsal and medial dorsal nucleus (of thalamus)
G and F Table 28-3
What Four Anatomic Sites of Damage had nothing listed under Other Neurological and Medical Finding?
- Basal Forebrain
- Fornix
- Anterior Thalamus
- Lateral Temporal cortex
