Neurophysiology Flashcards

1
Q

Transduction

A

-conversion of one form of energy into another

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2
Q

Fluid Mosaic Model

A

model of cell membrane

  • phospholipids, proteins, ion channels
  • lipid bilayer with embedded proteins
  • proteins can be relatively fixed or mobile in the plane of the membrane, extracellular, intracellular, or spanning (channels & pumps)
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3
Q

Channels

A
  • gated aqueous pores
  • contain gates which control whether ions can traverse the pore (regulated by movements of part of the channel in response to the gating stimulus)
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4
Q

Control Mechanism of Gates

A
  • transmembrane voltage
  • binding of ligand
  • temperature
  • mechanical distortion of the membrane
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5
Q

Selectivity Filter

A

a part of the channels which determined which ion types can move through the channel
-narrow portion or a charged region in the pore

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6
Q

Internal Binding Sites

A
  • allow modulation of channel function by signaling pathways
  • association with other molecules may modulate channel function & channel localization can be controlled by anchoring to the cytoskeleton
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7
Q

Electrical Consequences of Cell Membrane Structure

A
  • Ion Channels: resistive elements (conductors of ions)

- Lipid Bilayer: insulator (cf, dielectric of capacitor, stores charge)(capacitance) is RC circut

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8
Q

Ohm’s Law

A

V = IR

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9
Q

Resting Membrane Potential

A
  • membranes are semi-permeable to ions
  • at rest, neuronal cell membranes are primarily potassium permeable
  • selective permeability results in separation of charge which results in a transmembrane voltage
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10
Q

Concentration of Ions Intra & Extracellularly

A

-Na+ out
-K+ in
-Cl- passively distribute across the membrane
RMP = -70mV

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11
Q

Nernst Equation

A

Eion = 61 log [ion]o / [ion]i o=outside, i=inside

Ena+ = +5-mV Ek+ = -100mV Ecl- = -60mV

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12
Q

Nernst Equation

A
  • if membrane is at equilibrium & only permeable to a single ion species it can be described
  • predict what the membrane potential would be if the membrane became permeable to only a single ion species

Ex = (RT)/(zF) lin [x]o/[x]i

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13
Q

Goldman-Hodgkin-Katz equation

A

-predicts the membrane potential at equilibrium when all permeant ion species are taken into account

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14
Q

Membrane ATP Driven Ion Pumps

A

Na+/K+ pump is an ATPase: 3Na+ out, 2K+ in

Ca-ATPase transports Ca2+ ions across the cell membrane

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15
Q

Complicated & Varied Cell Geometry

A
  • distributed geometry, so not all membrane in the cell is isopotential at a given time
  • signals propagate through the neuron
  • passive RC properties of membrane set biophysical limits on this propagation of electrical signals
  • Active mechanisms (voltage-gated channels) are superimposed on these passive, or electrotonic properties of distributed membranes
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16
Q

Electrotonic Signal Propagation

A
  • passive movement of charge
  • time constant is longer for a larger cable diameter
  • amplitude decreases with distance
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17
Q

Hyperpolarizing

A

-events which enhance membrane potential - make the membrane more negative

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18
Q

Depolarizing

A

-stimuli which make the cell less polarized (less -, more +)

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19
Q

Large Depolarizing Stimuli

A

-cause a large, brief depolarization followed by repolarization (action potential), exceeded threshold of depolarization

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20
Q

Action Potential

A
  • arge, brief depolarization followed by repolarization

- active response that is due to activation of voltage-gated ion channels

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21
Q

Threshold

A

the voltage at which inward (depolarizing) current is just balanced by outward (hyperpolarizing current)

  • any further depolarization leads to the all-or-none AP response
  • balance b/w Na+ current and outward K+ currrent
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22
Q

AP rising Phase

A

up-stroke

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23
Q

AP falling Phase

A

downstroke (restoration of the original membrane potential = repolarization)

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24
Q

afterhyperpolarizatoin (AHP)

A
  • upon repolarization, membrane potential undershoots the original resting potential
  • “undershoot”, due to an inc. K+ conductance relative to original resting potential (delay of opening of K+ channels relative to Na+ channels)
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25
2 Major Types of Neural Electrical Signals
1) Graded Potentials | 2) Action Potentials
26
Graded Potentials
- passive responses, amplitude of the response is proportional to the amplitude of the stimulus (linear relationship predicted by Ohm's law) - Examples: receptor potentials (due to stimulation of a sensory receptor) & synaptic potentials (due to synaptic transmission) - analog response - no threshold, decrement with distance, small - not voltage sensitive, no refractory period
27
Action Potentials
- active responses (voltage-dependent) - threshold, above which the amplitude of the response is sterotyped (all-or-none), large, brief - digital response, regenerative
28
Ionic Basis for Action Potential: Upstroke
-due to an increase in membrane permeability of Na+
29
Ionic Basis for Action Potential: Downstroke
-due to inactivation of Na+ channels as well as activation of voltage-gated potassium channels
30
3 States of Channels
- Closed - Activated (open) - Inactivated - controlled by transmembrane voltage
31
Channel state at hyperpolarized potentials?
negative to -60mV - Na+ channels will be closed, will not conduct Na+ ions but are available to be activated by depolarization - all will be opened at 0 (depolarized)
32
Activation
-process of going from the closed to open state
33
Deactivation
-process of going from opened state to closed state (if time the membrane is depolarized is brief (<1ms), the channels may transit back from the open to closed state)
34
Inactivation
- continued depolarization causes open channels to be inactivated - process of going into teh inactivated state (possible to enter from closed state too) - no ions are conducted through the channel and the channel is not available to be activated by another depolarization
35
Remove Inactivation
- transition from inactivated state to closed state - a finite time at a negative membrane potential is required - only after channels are back in closed state are they once again available to be activated
36
States for Repolarizing K+ channels
- no inactivation time, only closed and activated (open) - resting potential: most are closed - depolarization: more K+ are open (activation), process is slower than in Na+ channels and occur at relatively more depolarized potentials than Na+ channels (facilitate attainment of threshold and underlie the afterhyperpolarization) - repolarization results in channel deactivation & re-entry into the closed state (deactivation)
37
Relative Refractory Period
- after AP, time period over which it requires a larger second stimulus to elicit another AP - due to the increased K+ permeability (that often causes afterhyperpolarization) following the AP
38
Absolute Refractory Period
- during which time, no stimulus, no matter how large, can elicit an AP - too many Na+ channels are in the inactivated state to allow attainment of the voltage threshold for an AP
39
Signaling by APs
- rapid signaling, without decrement over distance - as signal travels away from point of stimulus, it remains the same amplitude b/c it is regenerated in each patch of membrane that reaches threshold - more efficient than graded (electrotonic or passive) potentials at propagating signals over long distances
40
AP Propagation
- as each patch of membrane is depolarized to threshold, an AP is produced which electrotonically propagates to the adjacent patch of membrane - normally short, & AP current large, thus decrement of the signal is minimal b/w patches of membrane & the new patch is brought to threshold - typically initiate at 1 point (generally axon initial segment or 1st Node of Ranvier) & propagate along the axon as well as back into the soma & dendritic tree
41
What would happen if AP stimulus would occur in the middle of a cable?
-propagation would be bidirectional from the point of stimulation
42
Propagation of AP within the Axon
-usually unidirectional due to Na+ inactivation & the resulting refractory perior
43
After a given patch has an AP?
- it is normally refractory for a few ms, thus the AP only brings the next patch of membrane (in the direction of movement) to threshold - APs do not go one way and then turn around and go another
44
Conduction velocity of an Axon
- rate of advance of AP - increased by increasing the diameter of the axon (more charge, more surface area, less is lost) - myelin inc. conduction velocity
45
Myelin
- lipid that is wrapped around the axon in a glial cell membrane (Schwann cell:PNS, Oligodendrocytes:CNS) - inc. resistance of of the membrane for ions (since ions can't pass through lipid & typically axons do not place channels in regions under myelin) - inc. lipid thickness dec. the ability of the membrane to act as a capacitor (dec. cap. means less charge is stored on the membrane so more charge is available to pass through the axoplasm to the next node of Ranvier - inc. conduction velocity by restricting the ionic changes leading to APs to the Nodes of Ranvier & faciliting the movement of charge from one node to the next
46
Nodes of Ranvier
-interruption of myelin sheath by unmyelinated membrane areas
47
Action Potential Conduction in Unmyelinated Axon
- an AP occurs at a given patch of membrane - charge electrotonically (passively) propagates to next patch - if this depolarization reaches threshold, an AP is generated in new patch - Na+ inactivation causes refractory period which prevents AP from reversing directions - the conduction velocity of an unmyelinated axon is proportional to axon diameter (large diameter leads to greater velocity)
48
Action Potential Conduction in Myelinated Axon
- conduction velocity is. inc. by restricting the AP to the Nodes of Ranvier and by facilitating electrotonic movement of charge b/w nodes - inc. the resistance of the membrane to leakage of ions & dec. the capacitance of the membrane - AP seems to jump b/w nodes "saltatory conduction" - Na+ inactivation is more important than K+ activation for repolarization of APs
49
Spike Initiation Zone
-in neurons its either at the axon initial segment or the 1st Node of Ranvier due to combo of high Na+ channel density & geometric factors
50
Multiple Sclerosis
- loss of myelin sheath of some axons (demyelination) - underlying mechanism: inflammation - initially leads to conduction block b/c the Na+ channels are located too far apart for passive mechanisms to result in depolarization of the next group of channels (old Node) - distribution can be remodeled, restoring some degree of axonal function
51
Channelopathies
-mutations in channels which alter function & lead to pathology
52
Alpha subunit amino acid sequence
- characterized by 4 domains (I-IV), each consisting of 6 transmembrane spanning regions - 4 domains arranges so as to form the aqueous pore b/w them - when specific amino acids are mutated, this leads to different types of channelopathy
53
Point mutations in Sodium Channel Alpha Subunit
- lead to disease - cause generalized epilepsy with febrile seizures (GEFS) cause slowed inactivation of Na+ channels (the channels remain open too long leading to hyperexcitablity)
54
Myotonia & Periodic Paralysis
-caused by Na+ channel mutations in skeletal muscle (neurons are not the only excitable cells)
55
Voltage-Gated Calcium Channel Alpha Subunit
- similar to Na - 4 domains of 6 transmembrane regions - several distinct types exist in the brain and other excitable tissues - mutations can lead to channelopathies
56
Familial Hemiplegic Migraine
-associated with mutation of P/Q-type Ca2+ channels (CaV2.2: gene name CACNA1A)
57
Episodic Ataxia Type 2
-due to truncation mutants of Cav2.2 Ca2+ channels`
58
CSNB
-due to truncated L-type Ca2+ channels in the retina (alters sensitivity of the channels to modulation by calmodulin)
59
Lambert-Eaton syndrome
- small cell carcinomas produce abs to voltage-gated Ca channels (P/Q type) - autoimmune activity alters Ca channel function - clinical manifestations: dysfunction of neuromuscular junction
60
BFNC - Benign Familial Neonatal Seizures
-most prevalent known cause of BFNE is mutation of KCNQ2 (voltage-gated potassium channel)
61
Myotonia
- hyperexcitability of muscle - mutations in voltage-gated Cl- channel - resting membrane potential of muscle fibers becomes relatively depolarized, making them more excitable
62
Episodic Ataxia Type 1
-mutations in Kv1.1 type potassium channels in Purkinje cells