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Flashcards in Physiology Deck (58)
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1
Q

What is neuromodulation?

A

A substance that modifies the sensitivity of synaptic stimulation or inhibition by acting on a neuron

2
Q

What are the 4 classes of neuromodulators?

A
  1. Esters
  2. The amines
  3. Amino acids
  4. Gases
3
Q

List the neuromodulators under each class

A

Class I: Esters
Acetylcholine

Class II: The Amines
- Catecholamines:
Dopamine, norepinephrine, epinephrine,
-Serotonin, Histamine

Class III: Amino Acids
Glutamate
Aspartate
γ-Aminobutyric acid (GABA) 
Glycine
Class IV: Gases
Nitric oxide (NO)
4
Q

What are the classes of neurotransmitters?

A
  1. Amine (main)
  2. Amino acids
  3. Neuropeptides
  4. Purines and pyrimidines
  5. Gases
  6. Lipids
5
Q

List some lipid neurotransmitters

A

Anandamide, prostaglandins and neurosteroids

6
Q

List some gases as neurotransmitters

A

NO and CO

NB: NO are in postsynaptic neurons and modify the length of excitablity

They may play a role in memory

7
Q

List some neuropeptides

A

Substance P, Vasopressin, endorphins, neurotensins

8
Q

Where are neuropeptides synthesized?

A

By ribosomes in the neuronal cell body

9
Q

Compare the action, storage of the amines, amino acids and neuropeptides

A

Amines are rapidly acting and they act on ion channels. They are stored in small dense vesicles.

Amino acids are rapidly acting and act on ion channels as well. They are stored in small clear vesicles.

There is reuptake and recycling of vesicles by both amino acids and amines

Neuropeptides are slow acting and are stored in large dense vesicles. They act through second messenger systems to cause long term changes in metabolism of neuron.

10
Q

What is the purpose of Ca2+ in neurotransmitter release?

A

Ca2+ is needed in synaptic vesicle budding, fusion and discharge

11
Q

What is the purpose of clathrin?

A

After neurotransmitter release, the vesicular membrane is coated with the protein clathrin - identifying it for recycling.

The clathrin coated pits are transferred to the endosome, where the membrane is reused for new vesicles and refilled with neurotransmitter.

12
Q

What are ionotropic NT receptors?

A
  1. Ligand gated ion channels– NT binding causes ion pore or channel to open
  2. Fast neurotransmission
  3. Short-lived response
  4. Inhibitory NTs cause Cl- influx and hyperpolaristion
  5. Excitatory NTs cause Na+ influx and depolarisation

E.g.: nAchR, GABAA, glycine and glutamate (AMPA/NMDA/Kainate) receptors

13
Q

What is the difference between cation and anion ionic channels?

A

Cation channels are lined with negative charges. Allow mainly Na+ ions to pass but sometimes K+ or Ca2+ ions. These channels are excitatory

Anion channels are lined with positive charges. Allow mainly Cl- ions to pass. These are inhibitory transmitters

14
Q

What are metabotropic NT receptors

A

•NT binding activates G protein which then activates channels or second messenger systems
• Slow neurotransmission
• Longer duration of action
• E.g.: mAchR, D1/D2,
adrenoreceptors, most 5-HT receptors, mGluR, GABAB

15
Q

What is the difference between metabotropic and ionotropic NT receptors?

A

Ionotropic NT receptors have fast neurotransmission and short-lived responses. It opens directly on NT binding. Can be inhibitory or excitatory,

Metabotropic NT receptor has slow neurotransmission and longer duration of action. On binding to metabotropic receptors (G-protein) it will activate other channels or second messenger systems.

16
Q

Where is serotonin found?

A

In the raphe nuclei located in the brainstem

17
Q

What is the name of the glutamate transporter that removes glutamate?

A

EAAT

18
Q

List the glutamate receptors for excitatory effect

A

• Ionotropic
– NMDA
– AMPA
– Kainate /quisqualate

• Metabotropic
– mGluR (1-8)

19
Q

Function of NMDA receptor

A

Requires both ligand (neurotransmitter) and depolarization to open.

Blocked by Mg2+

Depolarization displaces Mg2+ ions

Channel become permeable to Na+ and Ca2+ when Mg2+ is displaced

20
Q

Glycine is the main inhibitory NT in the spinal cord and brainstem but GABA is the main inhiboty NT in the>

A

Brain, primarly found in interneurons

21
Q

Glutamate is a major excitatory NT and is synthesized from glutamine by glutaminase.

Which inhibitory NT does glutamate form?

A

GABA via glutamic acid decarboxylase

22
Q

GABA and glutamate are stored in small clear vesicles. What are they packaged in?

A

GABA is packaged into VGAT vesicles.

Glutamate is packaged into vGlut vesicles

23
Q

How are gaba and glutamate removed?

A

Reuptake into nerve terminals or glial cells by specific membrane transport systems

  1. GABA reuptake into nerve terminals for recycling
  2. Glutamate uptake by glia
24
Q

What are the two types of GABA receptors?

A

GABA-A and GABA-B

25
Q

Differentiate b/w GABA-A and GABA-B

A
• GABA A
– Ionotropic
– Chloride channel
– Activation causes hyperpolarization
– Other agonists: BZDs, barbiturates.
• GABA B
– Metabotropic
– Leads to increased efflux of K+
and hyperpolarization
– Also leads to decreased
presynaptic Ca2+ influx
– Agonist: baclofen, ?gabapentin
26
Q

Where is gylcine synthesized from?

A

Serine

27
Q

Glycine is taken up by?

A

GLYT transporters

28
Q

What is the antagonist to glycine?

A

Strychnine

29
Q

Types of glycine receptors

A

α, β:
– Ionotropic
– Chloride channels
– Hyperpolarization

30
Q

Where are enkephalins and dynorphins found?

A

found in the periaqueductal gray and dorsal horn of spinal cord

31
Q

What are the functions of enkephalins and dynorphins?

A

inhibit the flow of pain information to the brain.

They are endogenous opiod peptides

Receptors are Mu, kappa and delta

32
Q

Where are endorphins found?

A

In the hypothalamus

33
Q

Which family does substance p belong to?

A

Tachykinins

34
Q

Where is substance P found?

A

Found in:

  1. Primary afferent nerve endings (C fibres),
  2. Substantia gelatinosa of cord,
  3. Substantia nigra
35
Q

What is the receptor of substance P?

A

neurokinin-1

36
Q

What is the role of substance P?

A

pain transmission / inflammation, nausea,

mood/depression, migraine

37
Q

Dopamine binds to

A

dopaminergic receptors of substantia nigra of midbrain and hypothalamus

38
Q

What is peroxyanitrite?

A

Combination of NO and superoxide anions (O2-) –> peroxynitrite (ONOO-)

Peroxynitrite is an oxidizing free radical that can cause DNA fragmentation and lipid oxidation

Plays a role in memory through Long Term Potentiation in the hippocampal formation.

39
Q

In hypoxia Cortical areas are more sensitive to hypoglycaemia than the vegetative centers of the brain stem

A

In hypoxia Cortical areas are more sensitive to hypoglycaemia than the vegetative centers of the brain stem

40
Q

Energy needed in the brain for what purpose?

A

Maintain the ionic gradient across nerve membranes. Ionic transport in the neurons mainly to transport Na+ and Ca2+ to the outside an K+ to the inside

Oxidation of non-glucose substrates
ketones/lactate during prolonged fasting.

41
Q

High metabolic rate , hypoxia to brain for more than 10 sec causes unconsciousness

A

High metabolic rate , hypoxia to brain for more than 10 sec causes unconsciousness

42
Q

How does glucose enter the brain?

A

via GLUT 1 in cerebral capillaries

Insulin is NOT required for cerebral cells to utilize glucose

43
Q

Where is glycogen stored?

A

primarily stored in astrocytes

44
Q

During prolonged starvation, beta-hydroxybutyrate and acetoacetate replaces glucose as the predominant fuel for brain metabolism

A

During prolonged starvation, beta-hydroxybutyrate and acetoacetate replaces glucose as the predominant fuel for brain metabolism

45
Q

What is the purpose of glut 1 and glut3 and 5?

A

GLUT1 :localized in microvessels of the blood-brain barrier. Moves glucose from the capillary lumen to the brain interstitium.
GLUT3 / GLUT5: transport glucose from interstitium into neurons and glial cells.

46
Q

P-glycoprotein

A

Transport various proteins and lipis across membrane via ATP binding

47
Q

What is the purpose of Na+K+2Cl- co-transporter?

A

It is stimulated by ET-1 and ET-3 (ET-endothelin).

Helps keep brain K+ concentration low

48
Q

What is the body’s response to hypoglycemia?

A

Hypoglycemia is recognised in the ventromedial hypothalamus (glucose sensor)

Epinephrine: Triggered at ~70 mg/dL of blood glucose. Accompanied by many classic symptoms of hypoglycemia – shakiness, trembling, nervousness, and tachycardia.

In type 1 or type 2 diabetes, glucagon secretion becomes defective, epinephrine secretion becomes the critical counterregulatory factor.

49
Q

What is the multiorgan effect due to hypoglycemia?

A

Multiorgan effects

(1) drives glycogenolysis,
(2) stimulates gluconeogenesis in the liver and kidney,
(3) decreases peripheral glucose uptake,
(4) stimulation of lipolysis.

50
Q

What is the function of growth hormone/cortisol on hypoglycemia?

A

It is a slow acting hormone , acts 3hrs after hypoglyemia

Functions:

(1) systemic glucose production
(2) suppressing peripheral glucose oxidation and use
(3) lipolysis.

51
Q

What is the function of the liver in hypoglycemia?

A

(30 to 35 mg/dL), in the absence of counterregulatory hormones. (glycogenolysis and gluconeogenesis ).

52
Q

At a level of 76 - 72 mg/L of glucose in the blood which hormone is suppressed?

A

Insulin

53
Q

At 67mg/dL which hormones are increased?

A

Counterregulatory hormones of insulin are increased i.e glucagon, epinephrine, and growth hormone/cortisol

54
Q

What are the effects of ammonia on nerve cells?

A

Ammonia is very toxic to nerve cells.

Ammonia toxication is believed to be a major cause of the bizarre neurologic symptoms in hepatic coma.

55
Q

What makes ammonia toxic to the nerve cells?

A

It reacts with ketoglutarate to form glutamate. The resulting depleted levels of -ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons.

56
Q

Rises in cerebral blood flow due to hypoxia, hypercapnia (raised blood CO2) will cause a rise in ICP

A

CBF is maintained by the process of autoregulation.

The normal cerebral blood flow is 45-50ml100g-1min-1,

when the flow falls to less than 18-20ml100g-1min-1, physiological electrical function of the cell begins to fail.

57
Q

What are the energy requirements for white vs gray matter?

A
  1. White matter: 20-50ml/100g/min

2. Gray matter : as high as 100ml/100glmin

58
Q

Brain maintains cerebral blood flow through autoregulation. What is autoregulation?

A

Autoregulation is a change in cerebral perfusion pressure resulting in a compensatory change in vessel caliber.

A drop in CPP produces vasodilatation
A rise in CPP produce vasoconstriction