Voltage Gated Ion Channels Test 2 Material

Front 1

Describe a Voltage Gated Ion Channel

Back 1

Structurally similar to a ligand gated channel. Channels open and close in response to the changes in the membrane potential. Comprise populations on cell membrane and alter membrane potential.

Front 2

Describe the Na Voltage Gated Channel

Back 2

One Alpha subunit and 2 or 3 Beta subunits

The Alpha subunit has a 4 homologous transmembrane domain around a central pore, w/ each containing 6 alpha helics.

The inactive particle lies b/w domains 3 and 4 and the voltage sensor is on the 4th helix of each domain.

Front 3

What are the blockers of the Na channel?

Back 3

TTX (Tetrodotoxin) ansd STX (saxitoxin)

Front 4

What are the Na channel inactivation blockers?

Back 4

Batrachotoxin (BTX), Scorpion toxin (alpha- and beta-Sc TX), and Anemonne Toxin (ATX)

Front 5

What are the K channel blockers?

Back 5

Tetrahyammonium (CH3CH2)4 NCl

Front 6

General Characteristics of a Voltage -Gated Channel

Back 6

1. Highly Ion-specific

2. Respond to changes in Em

3. Opening may be rapid or delayed

4. Closure is automatic

5. Blocked by specific agents

Front 7

What are the techniques for studying ion channels?

Back 7

1. Voltage Clamp Method

2. Patch Clamp Method

Front 8

Describe the voltage clamp method.

Back 8

The potential is kept at a constant rate by the electronic feedback circuit across the membrane. Any change in the potential is offset by an opposite bucking current to maintain the clamped value.

Front 9

How is the bucking current recorded?

Back 9

As an accurate reflection of any ionic current (ex. ion flow)

Front 10

Describe the Patch Clamp Method

Back 10

Similar to voltage clamp method but at the level of channels. A narrow pipette isolates tiny sections of membrane (<1microM) and it is records currents from 1 or more channels.

Front 11

What are the basic steps in channel opening/closing?

Front 12

What is conductance?

Back 12

A function of ion channels that indicates how readily an ion can move in a circuit.

Front 13

If Na could become permeable then its _____ would change 1000x.

Back 13

Conductance

Front 14

What are the two types of propagation?

Back 14

Electronic conduction- short distance conduction w/ decrement

Action potentials- long distance conduction w/o decrement

Front 15

What are the 3 key elements that all nerve impulses rely on?

Back 15

1. (Active transport of ions) to generate asymmetric distributions across the plasma membrane.

2. Reservoir of potential energy in the form of a (transmembrane electrochemical gradient.)

3. (Dramatic change in membrane potential) (Vm) when the gradient drives ions thru ion-selective channels.

Front 16

____ carry local electric currents by simple diffusion alone.

Back 16

Ions

Front 17

What are the characteristics of electrotonic conduction?

Back 17

1. Local currents carried by ions

2. Follow electrochemical gradients

3. High velocity

4. Rapid Attentuation (1-3mm max)

5. Lack amplification

6. Occur regionally in all neurons (soma, internodes, dendrites)

7. Some neurons only have electrotonic conduction

8. Increased stimulus= increased Na voltage gated channels= increased graded potential

9. Summative

10. Graded potential are infinitely variable in size, shape and duration.

Front 18

What is an action potential?

Back 18

a large, brief change in the membrane potential that is propagated along the length of an axon w/o decrement

Front 19

What are the genera properties of action potentials?

Back 19

1. Threshold- minimum degree of depolarization b/4 the event become regenerate

2. All-or-None Responses- generally equivalent in shape (amplitude & duration) except during relative refractory period.

3. Latency- The time b/w initiation and peak amplitude. Indirectly proportional to stimulus strength

4. Strength-duration relationship- AP formation based on size and duration of stimulation @ the axon hillock

5. Refractory Periods- interval following an AP in which stimulus fails to generate a 2nd AP

6. Accomodation- time dependent decrease in excitability; sensitivity or habituation?; Threshold increases following repeated sub-threshold depolarizations

Front 20

Importance of the refractory period?

Back 20

Discrimination / sensitivity

Front 21

What is the difference between absolute and relative refractory periods?

Back 21

Ab RP: NO AP is possible

Relative RP: Larger stimulus needed for a weaker AP

Front 22

The Hodgkins Cycle

Back 22

n

Front 23

What are the changes in conductance during an Action Potential?

Back 23

1. Patch and voltage clamp studies

2. Movement of the ion x reflected in change of conductance:

Inward flux of Na corresponds to rising phase (Depolarization)

Outwar flux of K corresponds to the falling phase (repolarization and hyperpolarization)

Front 24

Model system for the pioneering studies of Hogkin and Huxley?

Back 24

Giant axons of Loligo Pealei

Front 25

Why did they use the Loligo Pealei as a model system?

Back 25

1. Permit uniform contraction of mantle activity

2. Diameter permitted use of large handmade electrodes

3. Perfused evacuated axons using Na isotopr and channel blockers

Front 26

Hodgkin and Huxley published a book that is the foundation of our understanding of AP, what was it?

Back 26

A math model of Action potential. They won a Nobel prize for medicine.

Front 27

____ is a function of the length constant

Back 27

Velocity

Front 28

What are the 2 evolutionary strategies to maximize the speed of conduction ?

Back 28

Increase Axon Diameter

Combine 2 types of Propagation

Front 29

What is it called when you combine the two types of propagation?

Back 29

Saltatory Conduction

Front 30

What is Saltatory Conduction?

Back 30

The speed of electronic transmission coupled with propagation without decrement of AP. The AP alternates with ET or nodes of ranvier and internodes.

Front 31

Why is it that impulses travel in one direction?

Back 31

Refractory Period

Front 32

Advocate of the early belief (reticular theory of the synapse).

Back 32

The entire nervous system is composed of a single continuous network- Camillo Golgi

Front 33

Advocate of the Neuron Doctrine. Proposed that neurons are not continuous but made up of discrete individual cells.

Back 33

Demonstrated Gaps by silver staining- Ramon y Cajal

Front 34

The term synapse was coined by_____ considered the founder of modern neurophysiology.

Back 34

Charles Sherrington

Front 35

What is a synapse?

Back 35

A junction across which a nerve impulses passes from an axon terminal to a neuron, muscle cell or gland cell.

Front 36

What are the 2 basic types of synapses?

Back 36

Electrical- Direct coupling via gap junctions

Chemical-Neuromuscular junctions

Front 37

Exponential attenuation may require ______ presynaptic signal.

Back 37

>1

Front 38

Gap junctions have channel proteins called ___ and and pores called ____

Back 38

connexins (verts) or innexins (inverts); Connexon or hemichannel

Front 39

Rectification empirically determined physiologyically relevant direction

Back 39

Orthodromic stimulation

Front 40

Rectification determines physiologically irrelevant direction

Back 40

Antidromic stimulation

Front 41

Examples of locations that rectification may occur.

Back 41

B/w receptor cells, cardiac muscle fiber, smooth muscle fibers.

vertebrate CNS or Retina

Escape reflex circuits of inverts

Front 42

What are the advantages of a Electrical Synapse?

Back 42

Faster than chemical synapses

Permits close synchrony of effectors

bidirectionality possible

Front 43

What are the disadvantages of Electrical synapses?

Back 43

Fine integration not feasible

excitatory only

difficulty innervation large effectors

Front 44

___ can increase or decrease # of postsynaptic ion channelsand modify the sensivity of the postsynaptic membrane.

Back 44

NT

Front 45

What is the most common type of synaptic locations ?

Back 45

Axodendrodritic and Axosomatic

Front 46

What synaptic location is usually electrical?

Back 46

dendrodendritic

Front 47

What synaptic location is usually near presynaptic terminus to regulate NT release via Ca?

Back 47

AxoAxonic

Front 48

Difference between axon varcosities and Enpassant synapse?

Back 48

Both are beadlike arrangements of axon swellings in the CNS. Varcosities have postsynaptic membranes unspecialized and w/o increased receptors

Enpassant have postsynaptic membranes specialized and w/ increased receptors

Front 49

describe spine synapses

Back 49

dendrites rich in postsynaptic densities. Microfilaments allow changes in size and shape therefore permitting plasticity in #s and strength of synapses.

Front 50

synaptic vesicles occur in what two distinct populations?

Back 50

storage pool 80% and releasable pool 20%

Front 51

Describe the storage pool

Back 51

bound to actin filaments of cytoskeleton and cannot migrate until freed by Ca

Front 52

Describe the releasable pool

Back 52

Bound to the active zones of apical presynaptic membranes that contain specialized proteins for synaptic vesicle attachment and exocytosis and voltage gate Ca channels

Front 53

Calcium trigger what two events for NT release?

Back 53

vesicle mobilization from the storage pool and vesicle fusion from the releasable pool and exocytosis.

Front 54

Difference between Fast/Direct and Slow/Indirect Synaptic Transmission

Front 55

What is the reversal Potential?

Back 55

The change in the psp falls somewhere between the equilibrium potentials for 2 ions if the 2 ions are premanent. sum of the synaptic currents (psp upon synaptic stimulation)

Front 56

If Erev >Em then the psp is ____

Back 56

excitatory

Front 57

If the Erev< Em then the psp is _____

Back 57

inhibitory

Front 58

What 3 criteria must be met to warrant NT status?

Back 58

1.Must elicit the same physiological effect in the postynaptic membrane as does presynaptic stimulation

2.Must be released during presynaptic activity

3. Must be blocked by the same substances that block natural transmission at the synapse

Front 59

What are the classification schemes of NT?

Back 59

chemical structure and mechanism of action

Front 60

Describe the NT of Fast Direct transmission.

Back 60

1st to be characterized: few in #s. Ionotropic or metabotropic

Front 61

Describe Ach

Back 61

released from cholinergic neurons; Nicotinic receptors (ionotropic; fast excitation)

Muscarinic receptors (metabotropic; slow; inhibit/excite)

Front 62

Define Agonist and Anatgonist

Back 62

Agonist: bind receptor and mimic ligand response

Antagonist: bind receptor w/o ligand response; blocks natural ligand

Front 63

What are AchE inhibitors?

Back 63

developed by Bayer chemical company germany WWI.

Function- nerve gas (japan WWII) interruption of nmj (respiratory)

Antiodote - Atropine

Front 64

NT that is usually ionotropic abd excitatory with only 1 subclass that is metabotropic?

Back 64

Glutamate

Front 65

japanese word meaning the essence of of taste

Back 65

ajinomoto

Front 66

Tokyo university chemist that iolsted a white salt from kombu to how it give s meaty flavors?

Back 66

Kikunae Ikeda

Front 67

What is Umami?

Back 67

one of the 5 basic tastes sensed by specialized receptor cells present on the human tongue

Front 68

A NT that is a major inhibitory NT of the CNS ( ionotropic and metabotropic) and derived from glutamate va decarboylation at C gamma.

Back 68

GABA

Front 69

Describe the NT of slow Indirect Transmission

Back 69

Fast axonal transport; diverse group of compounds and all operate via metabotropic receptors

Front 70

what are the 2 main division of compounds for NT of slow indirect transmission

Back 70

biogenic amines (AA derivatives) - 4 members and peptides- largest mot diverse group

Front 71

This slow NT affects both the CNS and PNS; is excitatory and inhibitory and has 2 major classes of adrenergic receptors (alpha n beta)

Back 71

Norepinephrine

Front 72

This slow NT affects the CNS; is excitatory and inhibitory ;1st implicated by neurological dysfunctions: parkinson's disease, schizophrenia

Back 72

Dopamine

Front 73

What is Parkinson's disease?

Back 73

Degeneration of dopaminergic neurons of the substantia nigra of the brain stem. DOpamine cant pass through the blood barrier so L-Dopa is used instead.

Front 74

What is Schizophrenia?

Back 74

group of mental disorders marked by a variety of symptoms (therory- Dopamine imbalance)

Front 75

What are the evidences of overactive dopaminergic neurons in schzophrenia?

Back 75

Mescaline ( agonist induces behaviors)

chlorpromazine (antagonist is a powerful antipsychotic)

Front 76

This NT has multiple roles inthe NS; melatonin precusr in the pineal; decreased the activity og serotonergic neurons

Back 76

Serotonin

Front 77

Removal of biogenic amines from the synaptic cleft

Front 78

Describe peptides

Back 78

Acts as a NT and or neuromodulator and is often released as co-transmitters into the synapse. Synthesized as propeptides

Front 79

Why peptides more potent though they have less concentration than other NT?

Back 79

higher binding affinity

greater amplification via intracellular pathways

mechanisms terminating activity are slower

Front 80

Examples of peptides and describe each

Back 80

substabce p- mediation of pain

endorphins- endogenous opioids (allievate pain and sense of euphoria)

Neuropeptide- most abundant in the brain (feed behavior circadian rhtythmas and sexual function anxiet/stress response peripheral vascular resistance and contractility o fthe heart

Front 81

receptors in the ionotropic pathway

Back 81

Ach receptor- nicotinic: derived from muscle tissue so increased nmj means increased Ach receptors. In electric organs of teleosts and elasmobranchs. and irreversible binding of radiolabeled beta-bungarotoxin (high homology)

Front 82

____ act as trandsucers for receptors in the metabotropic pathways

Back 82

g proteins

Front 83

Describe the adrenergic receptors (metabotropic pathways)

Back 83

ligands = norepinephrine and epinephrine

2 major classes: alpha and beta; excitatory, inhibitory, tissue-specific and hormonal.

Front 84

Which subclass of adrennergic receptors has inositol phophilid pathway, activation of CA channels and flight or fight response

Back 84

alpha 1

Front 85

Which subclass of adrenergic receptors has cAMP signal transduction, inactivation of Ca channels and occur or presynaptic membrane (autocrine negative feedback)?

Back 85

alpha 2

Front 86

which subclass has cAMp signal transduction( excitatory via Gs), activation of Ca channels

Back 86

beta ;

beta 1- heart and cerebral cortex

beta 2 - bronchial dilation and cerebellum

beta 3- adipose lipolysis

Front 87

what is neural integration?

Back 87

coordinated actions of neurons to perform a behavior

Front 88

examples of neural integration

Front 89

3 neurons of the classical disynaptic reflex arc?

Back 89

sensory, interneuron, efferent

Front 90

Flexion requires depolarization of efferent axon hilllock which depends on ...

Back 90

distance of synapse from hillock

#s and frequency of presynaptic APs

Inhibitory vs excitatory synapses

Front 91

Define temporal summation

Back 91

synaptic events from a single presynaptic neuron occur close together in time

Front 92

Define spatial summation

Back 92

simultaneous activities of 2 or more presynaptic neurons

Front 93

What are the two types of modification of neuronal function as the result of experience?

Back 93

Homo- and Hetero- synaptic modulation

Front 94

What are the monosynaptic mechanisms that result in use dependent change in NT release? describe each. (homosynaptic)

Back 94

Synaptic Facilitation-increased NT release in response to repeated APs. Increased Ca release NT.

Synaptic depression- decreased NT in response to repeated AP. synaptic vesicle exocytosis rates exceed replenishment rates

Post-tetanic potentiation- increased amplitude of response follow tetanic stimulation of presynaptic neuron

Front 95

What are the monosynaptic mechanisms that result in use dependent change in NT release? Describe each. (heterosynaptic)

Back 95

presynaptic inhibition- inhibitory axoaxonic synapse reduces psp from excitatory synapse; subtle control of synaptic efficacy.

neuromodulation- a change in neuronal function caused by diffusing neuropeptides; lasts secs to min and affect adjacent and distant synapses; partially or hyperpolarizes psp

heterosynaptic facilation gill withdrawal reflex in aplysiaa californica

Front 96

____ is the most abundant NT in the body, persent in over 50% of nervous tissue.

Back 96

glutamate

Front 97

what are the 3 subclasses of ionotropic glutamate receptors?

Back 97

AMPA, NMDA, Kainate

Front 98

What happens during normal synaptic transmission of glutamate in long term potentiation?

Back 98

glu binds to both NMDA and AMPA receptors but only AMPA is affected and opens to permit the entry of cations. NMDA is blocked by Mg

Front 99

What happens during the early phase of LTP, high frequency stimulation?

Back 99

AMPA channels open leading to depolarizatio. as a result mg is dislodged from the NMDA receptor channels and Ca enters

Front 100

During the early phase of LTP, what Ca-dependent pathways does the Ca trigger?

Back 100

-Ca-calmodulin Kinase

- Protein Kinase C

-Tyrosine Kinase

Front 101

____ is known as the longest lasting process known to neuroscience

Back 101

LTP

Front 102

LTP may be the foundation of _______ via the formation of new synapses.

Back 102

Long term memory

Front 103

What is the process of synapse formation in LTP?

Back 103

-Ca-calmodulin kinase phosphorylates AMPA channels increasin g their sensitivty to glu.

-NO is synthesized and travels to the presynaptic terminal to activate guanylate cyclase

-cGMP is generated which stimulates an increased rate of glu exocytosis from the presynaptic neuron

-The transcription cascade results on the synthesisand insertion of NMDA and AMPA receptors.

-increased concentrationnof AMPA receptors promotes the formation of additional spine synapses.