Nerve Conduction Flashcards
Introduction to nervous system.
- The nervous system (NS) is complex and comprises neurons(10^11) and glial cells (10^12). Glia are non conducting supporting cells and essential ‘partners’
- Neurons have a great variation in structure & biochemistry and are also referred to as secretory cells
- Neurons are specially adapted to generate and propagate impulses.
NB basic morphology of the neuron = Cell body, hillock, axon, and dendrites
Functional zones of the neurons
Somato-dendritic zone - receive primary input
Somatic zone - integration and chemical encoding
Axon hillock zone - electrical encoding
Axonal zone - Signal propagation
Presynaptic zone = signal output
All cells are polarized, meaning?
- If you put a Recording device across cell membrane you’ll record potential difference or charge across the membrane = polarized
Nerve and muscle the polar nature changes transiently or over a short period of time
- Polarized cells are a characteristic of life.
- Polarity of excitable tissue changes when stimulated. This forms the basis of communication in NS.
The plasma membrane plays an instrumental role in this process.
The special role of the cell membrane.
The cell membrane is a continuous lipid bilayer with proteins.
-The lipid bilayer effectively separates two conducting media.
[ECF* & ICF# are electrolytic solutions]
- The bilayer is a non-conductor & acts as a dielectric.
- This geometric arrangement (ECF + Bilayer + ICF) approximates that of a capacitor
-A capacitor stores an electrical charge between the two plates. It also discharges.
A charge, therefore, exists across the membrane of each living cell.
……
Cell membrane perfect insulator.
Resting membrane potential
The charge or potential difference across the membrane is due to the separation of the 2 fluid compartments and the unequal distribution of ions across the cell membrane.
This is called the Resting membrane potential (RMP)
This potential difference varies amongst cell types but is often quoted as ~ -70mV
To maintain the resting membrane potential [or this potential difference]
To maintain this PD:
1) T° needs to be within the physiological range 2) Ionic imbalance maintained 3) Cell membrane needs to ~25 A° thick (d), constant in cells
NB capacitance, c = ε A /d
where A = area, d = distance, ε = dielectric constant
Mammalian neuron
More Potassium in intracellular fluid than extracellular
More Sodium in Extracellular fluid than intracellular
#Na you’re out, K you’re in
More chloride out than in
More calcium out than in
-Let’s not forget the large concentration of negative anions with the cell (106.5mM)
Ionic pumps
- To maintain RMP, constant gradients need to be maintained with respect to Na+, K+ & Cl- ions
- Gradients maintained by ionic pumps
- Na+ & K+ transported by a common transporter → Na/K pump (Na+/K+ ATPase)
- Consists – 2 subunits = α & β
-The α unit → specialized & spans membrane many times:
EC surface binds K+
IC surface binds Na+ + site for phosphorylation
The pump is sensitive to IC [Na+]. Na+ binds with the receptor intracellularly and induces a conformational change → cycle commences (ATP)
In the Na and K pump. The ins and outs
- For each stroke 3 Na+ exported and 2 K+ imported (3:2 coupling ratio)
- Each cycle of the pump there is a net loss of positivity from the cell hence referred to as an electrogenic pump.
- β unit is a glycoprotein that offers stability to the pump
- Alpha unit also has receptors on extracellular surfaces that bind with ligands/ substances e.g. ouabain + glycosides
The sodium-potassium pump is usually coupled with which exchange mechanisms.
This pump is often coupled with other exchange mechanisms :
1) Cl‾ levels maintained
Chloride- bicarbonate
exchanger → 1 Na+ + 1 HCO‾imported →1 Clˉ ion pumped out
2) Sodium – Calcium exchanger with a 3:1 ratio.
This is one of the important mechanisms that is targeted therapeutically in cases of heart failure.
Nernst to Goldman equations
Na+, K+, Cl- ions are “major” role players in establishing PD. 2 considerations:
1) Chemical gradient 2) Equilibrium (electrochemical + electrostatic)
The Potential Difference at equilibrium described by Nernst:
EMF = -61 log [conc. outside] / (divided by) [conc. inside]
Mammals: K+ = - 102 mV
Na+ = + 56 mV
Cl- = - 76 mV NB Nernst equation → considers single ion!
Membrane → ∆ permeability rates for different ions!
-
Goldman - Hodgkin - Katz (G-H-K)
The Goldman-Hodgkin-Katz (G-H-K ) derived with these considerations
vrest= rt / f In pk out +pna out+ pcl in divided all these ps opposite.
P = permeability, [ ] = concentration, R gas constant,
T = Temp in K, F = Faradays constant,
Note RT/F =constant = 61.5mV
Important points of GHK
- RMP depends on the concentration gradients and on the relative permeabilities to Na+, K+ and Cl-.
- The Nernst potential for an ion does not take membrane permeability into account.
- The GHK equation describes a steady-state condition, not electrochemical equilibrium.
- There is a net flux of individual ions, but no net charge movement.
- The cell must supply energy to maintain its ionic gradients.
An important consideration on the membrane and different types of channels.
Membrane contains:
Passive (leak) channels that are always open
Gated channels that open and close in response to stimuli – essential for nerve function
There are 3 types of gated channels:
- Chemically regulated channel
- Voltage-regulated channel
- Mechanically regulated channel
Voltage gating in ion channels
- Voltage-gated ion channels display a voltage sensor (transmembrane helix) containing a number of positively charged amino acids along one side of the helix.
- ∆ electrical potential across the membrane induces a conformational change in amino acids causing the voltage sensor helix to change its position, thereby affecting the pore dimension of the channel.
depolarization causes the opening of the ion channel
The action potential (AP)
Remember each cell is like a capacitor
The action potential is a transient change in membrane potential of nerve & muscle
Pioneering work was done by Hodgkin & Huxley using squid axons
Response of excitable tissue has distinct phases:
Note equipment
NB - scale of recording
Sequence of events during an AP
- Adequate stimulus (chemical, electrical, mechanical).
- Increased permeability of the membrane to sodium ions at the point of stimulation (sodium gates open).
- Na+ moves inward following concentration and electrochemical gradient. Rate?
- Transmembrane potential reaches zero. Membrane depolarizes.
- More sodium gates open (Hodgkin cycle) and the influx of positive ions reverse the polarity inside the membrane relative to the outside. The cell moves towards EMFNa=+56mv
- Inactivation gate closes (sodium gate cannot be clamped in open state!)
- The membrane’s permeability to Na+ ions decreases, (sodium gates close), and its permeability to potassium ions increases (K+ gates open).
- K+ ions follow concentration and electrochemical gradient and move out of the cell, repolarizing the membrane. EMFK=-102mv
- Sodium and potassium pumps transport Na+ back out of the cell and K+ back into the cell.
Summary of events during an AP
-At Rest gK+»_space; gNa+, RMP =-70mv
(g =conductance)
- Threshold gNa+ > gK+
- Rising Phase PNa > 0mv (inward current), positive feedback on voltage gated Na channels. Inner gate inactivated.
-Falling Phase PK > PNa (outward current)
due to the opening of slow voltage-gated channels.
The all or non-law
- AP only occurs if the stimulus is of threshold intensity h
- The amplitude of AP is constant irrespective of stimulus strength
- The frequency of discharge is, therefore, an indication of the strength of the stimulus (stronger stimuli = more APs)
The Refractory period
-During an AP there are certain times when a 2nd stimulus will not produce another response
a) Absolute refractory period
- If a second stimulus is applied between firing level and ⅓ repolarization no second response produced
-This is due to the status of the Na channel!
b) Relative refractory period
- A second stimulus applied between ⅓ rd repolarization and hyperpolarization will result in a second AP being formed.
-Generally, the second stimulus has to be of greater intensity. (~20%). Why?
Changes in potential across the cell membrane can have two possible effects:
- Graded potential (chemically gated channels) gradually decreases or dies off along the length of the nerve
- Action potential is propagated along nerve viz nerve impulse (voltage-gated channels) [does not die or get weaker along the length of nerve]
Graded potential
A graded potential is a change in potential that is transmitted decrementally along membrane (decays)
Step 1: Membrane exposed to a chemical that opens the sodium ion channels
Step 2: Spread of sodium ions inside the cell membrane produces a local current that depolarizes adjacent portions of the cell membrane.
Propagation
- As an action potential develops in the initial segment, the transmembrane potential depolarizes to +30mV.
- A local current depolarizes the adjacent portion of the membrane to threshold.
- An action potential develops at this location, and the initial segment enters the refractory period.
- A local current depolarizes the adjacent portion of the membrane to threshold and the cycle is repeated.
Conduction of along the nerve
- AP occurs across a minuscule area/segment of membrane!
- During depolarization adjacent areas are ‘excited’!
Mechanism:
1. During depolarization, Na+ ions rush into cells (bring in ‘positivity’).
- Voltage along the inner surface of the adjoining membrane (distal) changes to threshold level AP initiated.
- This process repeated so new APs are propagated along the length of the fiber. A nerve impulse!
- Area proximal to AP is in the refractory period – the basis for unidirectional propagation of impulses.
Saltatory conduction
In the myelinated nerve the sheath insulates + increases resistance
Depolarization only can occur at nodes of Ranvier (Na+ and K+ voltage-gated channels found in high channel density
The influx of Na+ ions during depolarization at node serves as a “Local current” which changes voltage in adjacent node to threshold level → depolarization
Impulse effectively “jumped” hence saltatory conduction. Advantage –» impulses conducted more rapidly (X50-60).
Conserves energy!!
Interesting points to note
Anesthetics → alter nerve cells by disrupting the formation & transmission of nerve impulses.
Certain classes of local anesthetics (e.g. Novocain, Xylocaine) block Na+ channels and prevent action potentials along sensory neurons.
Some general anesthetics (ether, chloroform) open some K+ channels in the brain a bit wider than usual. This counter-acts the effects of gNa+ and prevents AP propagation.
Nerve poisons (e.g., scorpion venom) open Na+ channels and shut K+ channels, this ↓ gK+ hence disrupts AP.
Biphasic Action Potential
Remember the AP and RMP are recorded across the membrane with electrodes in ICF + ECF
- In laboratories, ECG, EMG & EEG recorded with electrodes on the surface of the body (so not RMP & AP!)
- The AP alters the electrical status of surrounding tissue
- Tissues around excitable are volume conductors.
- Depolarization wave is therefore recorded as it travels along the surface of the nerve/body.
Refer to diagram
Axoplasmic Transport
Neurons have unusual dimensions which poses logistical “issues” for bidirectional transport of various substances.
With specialized microscopy these transport mechanisms have been characterized as follows:
1) Fast anterograde flow – away from C.B.
2) Fast retrograde flow
3) Slow axoplasmic flow (anterograde)
NB. Defects in axonal transport are features of neurodegenerative disorders such as Alzheimer’s & Parkinson’s diseases + infections
1) Fast anterograde flow – away from C.B.
-Rapid ~400mm/day – transportation of organelles is a stop-and-go movement and “cargo” transported on a microtubule system* – movement mediated by kinesin KIF17 (molecular motor). Occurs independently of CB & electrical activity.
2) Fast retrograde flow
- Movement from the distal end to the cell body. Rapid at ⅔ speed of (1)
- Occurs on a similar microtubule system-mediated by dynein
- Advantages: components “recycled” (endosomes) & NGF*[nerve growth factor] transported to the cell body
- Disadvantages: neurotoxins and viruses (tetanus & herpes simplex) infect cell body.
3) Slow axoplasmic flow (anterograde)
- More complex 0.2 – 5 mm per day and involves special kinetic components. Details not characterized as others
- Small cellular components carried in this way
