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Neuroscience and NeuroAnatomy > 2 - Neuronal Ion Channels and Disease > Flashcards

2 - Neuronal Ion Channels and Disease Flashcards

1
Q

How many neurons are in our nervous system?

A

85 Billion

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2
Q

How many synapses are in our nervous system

A

Over 100 Trillion

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3
Q

Model Neuron Components

A

Input (Dendrites)
Integration (Dendritic Tree & Cell Body)
Action Potential Initiation (Axon Hillock)
Conduction (Myelinated Axon)
Output (Synaptic Bouton)

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4
Q

3 types of electrical signal responses from different neuronal populations

A

No Adaptation (Fire Continuously)
Adaptation (Fire, then slow their firing rate)
Pacemaker (No excitatory input required)

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5
Q

Ion Channels - 2 Essential Properties

A

Gating (Open or closed)

Permeation (Selectivity and conductance of ion flow through the channel)

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6
Q

4 types of Ion Channel gating

A

Voltage Gated
Ligand Gated (Extracellular Ligand)
Ligand Gated (Intracellular Ligand)
Stress Activated

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7
Q

Sodium Potassium Pump - Function

A

Keep K+ in and Na+ out

Keep inside more (-) than outside

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8
Q

Reversal Potential

A

The point at which Na+ no longer feels a drive into the cell

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9
Q

Potassium Channel Structure

A 
Tetramer
Each subunit has:
Intracellular N-Terminus
6 Transmembrane regions
Intracellular C-Terminus
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10
Q

On a Potassium Channel subunit, what senses the voltage change?

A

Transmembrane Regions 1 - 4

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11
Q

On a Potassium Channel subunit, what forms the pore, itself?

A

Transmembrane Regions 5 & 6

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12
Q

Sodium Channel Structure

A

Single subunit with long intracellular/extracellular regions dividing the channel into 4 domains that behave like a tetramer, even though they’re technically all connected.
Comes with lots of proteins and junk to regulate the channel’s activity

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13
Q

Calcium Channel Structure

A

Like a Sodium Channel. Four domains stitched together for the main pore-forming Alpha-1 Subunit, with auxiliary subunits (like Beta-1) crucial for getting the channel to the cell surface.

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14
Q

Why do Calcium Channels need a Beta subunit?

A

To reach the cell surface

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15
Q

Inward Rectifier Potassium Channels

A

Open in basal state. Think “leak channels” from Mowsh.

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16
Q

2 types of Voltage Gated Calcium Channels

A

Low Voltage Activated (T-Type)

High Voltage Activated (L-Type, P/Q-Type, N-Type, R-Type)

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17
Q

Nodes of Ranvier contain high concentration of

A

Voltage Gated Sodium Channels

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18
Q

Presynaptic Terminus contains high concentration of

A

Voltage Gated Calcium Channels

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19
Q

Diseases Linked to Calcium Channels

A

Autism
Epilepsy
Self-Biting Behavior
Neuropathic Pain

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20
Q

Diseases Linked to Potassium Channels

A

Long QT Syndrome
Paralysis
Diabetes

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21
Q

Diseases Linked to Sodium Channels

A

Long QT Syndrome
Epilepsy
Cardiac Arrhythmias
Pain

22
Q

4 main ways Voltage-Gated Ion Channels go bad

A

Mutations (Ion channelopathies)
Autoimmune Diseases
Defects in expression level
Mislocation within cell

23
Q

Painful Sodium Channelopathies

A 
Inherited Erythromelagia
PEPD
Overlap Syndrome
Channelopathy associated insensitivity to pain
Painful peripheral neuropathies
24
Q

Inherited Erythromelagia - Channel & Mutation

A

Nav1.7 - Gain of function, primarily enhanced activation

25
Q

Inherited Erythromelagia - Pattern

A

Pain - Distal limbs (intense burning & flushing)

26
Q

PEPD (Paroxysmal Extreme Pain Disorder) - Channel & Mutation

A

Nav1.7 - Gain of function, primarily impaired fast-activation

27
Q

PEPD (Paroxysmal Extreme Pain Disorder) - Pattern

A

Pain - Perirectal, periorbital, perimandibular

28
Q

Overlap Syndrome - Channel & Mutation

A

Nav1.7 - Enhanced activation + impaired fast-inactivation

29
Q

Overlap Syndrome - Pattern

A

Mixed

30
Q

Channelopathy associated insensitivity to pain - Channel & Mutation

A

Nav1.7 - Loss of Function

31
Q

Painful Peripheral Neuropathies - Channel & Mutation

A

Nav1.7 OR Nav1.8 - Gain of function, multiple effects on channel

32
Q

Painful Peripheral Neuropathies - Pattern

A

Early pain usually distal

33
Q

Painful Na Channelopathies - Typical Channel

A

Nav1.7

34
Q

Sodium Channel Speeds (In Health)

A

Fast Activation

Fast Inactivation

35
Q

Generalized Epilepsy with Febrile Seizures - Mutation

A

Altered channel inactivation (Alpha and/or Beta-1 subunits) causing persistent inward current

36
Q

Multiple Sclerosis - Proposed Mechanism

A

Demyelination disease
Sodium channels more widely distributed
Increased Nav1.6 sodium influx
Na+/Ca++ Exchanger compensates, leaving us with high intracellular calcium

37
Q

Kv7.1 Channels - Location

A

Heart & Inner Ear

38
Q

Leading cause of Long QT Syndrome

A

Kv7.1 Mutation leading to exertion-triggered cardiac arrhythmias

39
Q

Retigabine

A

Makes Potassium Channels unresponsibe, no longer fire action potentials

40
Q

M Channels

A

Regulated by Muscarinic Receptor activation

41
Q

Kv7.2 and Kv7.3

A

Heterotetramers that cause BFNS

42
Q

BFNS

A

Benign Family Neonatal Seizures - A loss of function mutation in potassium channels Kv7.2 and Kv7.3

43
Q

Queen of Ion Channels

A

Calcium Channels - Beyond contributing to the electrical properties of the neuron, they serve as the bridge between electrical and chemical signals

44
Q

Cav2.1 Channelopathies

A

Familial Hemiplegic Migraine

Episodic Ataxia Type 2

45
Q

Familial Hemiplegic Migraine

A

Migraines with weakness on one side of the body, can last up to weeks. From a Cav2.1 Channelopathy (missense mutation). Sometimes acompnaies by coma and ataxia

46
Q

Episodic Ataxia Type 2

A

Severe discoordination of motor activities. From a Cav2.1 Channelopathy via truncation or incorrect splicing, leading to a nonfunctional Cav2.1 channel.

47
Q

Cav1.2 Channelopathy

A

Timothy Syndrome

48
Q

Timothy Syndrome

A

Multisystem - Including Arrhythmias, Autism, Abnormal Facial Features, Webbed Fingers. From a subtle gain-of-function mutation in Cav1.2, allowing slightly more Calcium in after inactivation

49
Q

Opiate Analgesia Mechanism of Action

A

Acts on GPCR on presynaptic terminus, which sends 2nd messenger to inhibit Ca2+ channel.

50
Q

Medical Marijuana Mechanism of Action

A

Acts on cannabinoid receptors, which inhibit voltage-gated Ca2+ channels, reducing synaptic release.

51
Q

Target of Gabapentin

A

Alpha-2-delta subunit of Cav channels

52
Q

Gabapentin

A

Treats neuropathic pain and epilepsy

Neuroscience and NeuroAnatomy (41 decks)

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