NERVES AND MUSCLES VIVAS
Nerves
2011-2, 2010-1
Describe the resting membrane potential of a cell
- There is difference in electronic charge across a cell membrane
- The inside is negative compared to the outside
- Resting MP results from separation of positive and negative charges across a cell membrane
- Neuron average RMP -70 mV (about the equilibrium potential for K+)
What conditions are required to create a resting membrane potential
Across the lipid bilayer:
1. Must be an unequal distribution of ions across the membrane (creating a concentration gradient)
2. The membrane must be permeable to one or more of those ions (i.e. ion channels)
In a neuron what ions are involved and how is the concentration gradient produced
- K+ and Na+
- K+ is primarily intracellular and Na+ extracellular
- Passive movement of ions occur via selective ion channels
- More (leak) K+ channels open at rest so K+ is prime determinant of the RMP
- Na-K ATPase actively move ions against their electrochemical gradient to maintain RMP
2007-2, 2005-1, 2003-1
Draw and label an action potential of a neuron
1. RMP(-70mV);
2. Firing potential (-55mV)
3. Voltage gated Na channels open
–> Depolarisation and overshoot:
0mV -> +35mV
4. Na+ channels close (inactivated
state) and voltage gated K+
channels open (slower to open)
5. Na+ back to resting state
6. After-hyperpolarization (K+
channels slower to close)
7. K+ channels close -> RMP
2010-1, 2007-2
Describe the ionic fluxes during the action potential
Fast voltage gated Na channels - influx
- Rapid increase due to positive feedback
- Then repolarization by:
1. Rapidly to inactivated state (ARP)
2. Gradient reversed during overshoot
3. K+ channels open
Slower voltage gated K+ channels - efflux
- Negative feedback
- Slower to open and close
- Causes hyperpolarisation
- (which de-inactivates the Na-channels)
- Hyperpolarisation = RRP
2007-2
Where are ion channels distributed in myelinated neurons
- Voltage gated Na+ concentrated at nodes of Ranvier and initial segment of myelinated neuron
- Na+ channels are flanked by K+ channels involved in repolarization
2003-1
Discuss the factors that affect conduction
Myelinated vs unmyelinated
- Myelin, a protein–lipid complex that is wrapped around the axon
- Peripheral nervous system: Schwann cell wraps its membrane around an axon up to 100 times
- CNS most neurons are myelinated by oligodendrocytes rather than Schwann cells
- Unmyelinated: surrounded by Schwann cells without the wrapping of the Schwann cell membrane
A, B are mylenated, C are unmyelinated
Saltatory vs non-saltatory
- Myelinated nerves can conduct up to 50x faster
- The AP will jump (via a current sink) from node to node (of Ranvier)
Size
- Larger diameter = faster conduction
- Larger: proprioception, somatic motor function, conscious touch, pressure
- Smaller: pain and temp, autonomic function
Direction of the conduction
- Orthodromic conduction is natural synapse/receptor -> along axon -> to termination
- Antidromic is in the opposite direction – prevented by synapses (conduction only permited in one
direction)
Extra: “All-or-none” law
- Once the AP is generated it will have constant amplitude and form, no increase in stimuli
will change the AP (note- this is for a single neuron, no a nerve containing many)
Extras:
- Theshold intensity varies with duration - weaker need longer, stronger less time, as per strengthduration curve
- Slowly rising current may fail to generate AP due to adaptation
- Local response: subthreshold stimuli -> local electrotonic potentials
- Excitability is the reciprocal of threshold
- Absolute refractory period “occurs from the time of firing until repolarization is about 1/3 complete)
- Mixed nerves contain neurons of many sizes w/ different thresholds, a small stimulus -> small AP,
maximal stimulus -> maximal AP
2011-1
What are the different types of nerve fibres (What classifications are there)
Myelinated vs un myelinated
- Myelin, a protein–lipid complex that is wrapped around the axon
- Peripheral nervous system: Schwann cell wraps its membrane around an axon up to 100 times
- CNS most neurons are myelinated by oligodendrocytes rather than Schwann cells
- Unmyelinated: surrounded by Schwann cells without the wrapping of the Schwann cell membrane
A, B are mylenated, C are unmyelinated
Saltatory vs non-saltatory
- Myelinated nerves can conduct up to 50x faster
- The AP will jump (via a current sink) from node to node (of Ranvier)
Size
- Larger diameter = faster conduction
- Larger: proprioception, somatic motor function, conscious touch, pressure
- Smaller: pain and temp, autonomic function
Classifications
Gasser ABC (A – αβγδ), A and B myelinated, C unmyelinated
Numerical (sensory neuron) Ia, Ib, II, III, IV
- Aα (Ia) are large myelinated somatic motor or proprioception
- Aδ (III) are smaller pain and temp fibers
What is the clinical relevance to emergency medicine
Pain fibres are smaller and better penetrated by local anaesthetic leading to loss of pain before loss
of touch or proprioception
Susceptibilty to:
Hypoxia
Pressure
Local anaesthetic
Most
A
B
C
Intermediate
B
A
B
Least
C
C
A
Skeletal muscle
Definitions and Facts
Thick filament – myosin II, cross bridges w/ actin and have a catalytic site that hydolyses ATP
Thin filament – Actin in long double helix, w/ troponmyosin convering binding site at rest
Troponin T – binds the troponin to tropomyosin
Troponin I – inhibits the interaction of actin with myosin
Troponin C – contains the binding site for Ca2+
RMP of muscle -90mV
AP lasts 2-4ms, conducted at 5m/s, ARP 1-3ms, prolonged after-polarization
Sacroplasmic reticulum – membrane around cell, carries AP, stored Ca2+, involved in metabolism
T tubules – part of sarcotubular system, carries AP between the individual fibrils
Terminal cisterns – in close contact T tubules near A-I band junction
Isometric contraction – same length contraction
Isotonic contraction – same force
Eccentric contraction – the muscle lengthens as they contract
Because work = force x distance isometric does no work (and does negative work if eccentric)
Fibrillations – single fiber contraction due to denervation and increased sensitivity to circulating Ach
Fasiculations – contractions of a group of fibers due to pathologic discharge of spinal motor neurons
Motor unit – a single motor neuron and all the muscle is innervates (will be of the same type)
Size principal – recruitment is ordered, S before FR before FF
Metabolism:
O2 Debt
- Anaerobic metabolism allows more work
(6x) to be done than could otherwise if
completely dependent on O2 delivery
- After the period of exertion, the
accumulated lactate will be broken down
and ATP replenished by increased O2
consumption
- If lactate builds too high then enzyme
inhibiting pH will develop
Also: Creatine  (rest/exercise) phophorylcreatine  creatinine
2009-2, 2008-2, 2005-1
Describe the sequence of events in contraction and relaxation of skeletal muscle
2008-2, 2007-2
What is summation of contractions
1. The electrical response of a muscle fiber to repeated stimulation
2. Contractile mechanism does not have a refractory period, so repeated stimulation before
relaxation has occurred produces additional activation and a response added to the
contraction already present
3. With rapidly repeated stimulation, individual responses fuse into one continuous
contraction (tetanus; tetanic contraction)
4. Complete tetanus: no relaxation between stimuli; tension developed ~ 4 times that of an individual
twitch contraction
5. Incomplete tetanus: periods of incomplete relaxation between summated stimuli
Nb: stimulation frequency determined by the twitch duration
- so if twitch duration = 10ms, <100/s discrete responses, >100/s will cause summation
How does tetanus differ from Treppe 2007-2
Treppe (which means staircase in German)
- Series of maximal stimuli at a frequency just below tetanizing -> increasing tension between each
twitch
- Due to increased Ca2+ availability in sarcoplasm
- Cause for the force-frequency relationship in myocardial contractility
What are the major differences in types of skeletal muscle 2007-2
- slow and fast, containing a mixture of type I, IIa and IIb
- fast fibers may have twitch duration ~7.5ms, for fine, rapid precise movements
- slow fibres may have twitch duration up to 100ms, for strong, gross sustained movements
Other name
Colour
Myosin ATPase
Ca2+ pumping
Diameter
Glycolytic Capacity
Oxidative Capacity
Motor Unit
Type I (SO)
Slow oxidative red
Red
Slow
Moderate
Small
Moderate
High
Slow (S)
Type IIa (FOG)
Fast oxidative glycolytic
Red
Type IIb (FG)
Fast glycolytic
White
Fast
High
Large
High
Moderate
Low
Fast fatigue resistant (FR) Fast fatigable (FF)
Cardiac muscle
RMP -90mV
AP – depolarization 2ms, but very long plateau and repolarization 200ms (contraction half over)
Intercalcated disks – Connect interdigitated cells for strength
Gap junctions - Low resistance bridges for excitation as a syncytium (but no cytoplasmic connection)
T tubules are at Z lines (c.f. skeletal at A-I junction)
0 - Rapid depolarization, INa opens, fast Na+ influx
1 - Rapid initial depolarization, INa closes
2 - Plateau phase, Ca2+ influx (slow)
3 - Slow repolarization, IK , K+ efflux (slow)
4 - RMP
ARP is thus long – 200ms, and RRP until phase 4
This prevents tetany
Smooth muscle
2007-1
Describe the sequence of events in contraction and relaxation of visceral smooth muscle
Smooth muscle (vs skeletal)
- No striations, instead dense bodies
- Tropomyosin, no troponin
- Isoforms of actin and myosin are different
- Unitary (visceral): large sheets, gap junctions, syncytial
(e.g. hollow viscera: intestine, uterus, ureters)
- Multiunit: individual units, no gaps, en passant nerve endings to
each cell, for fine (non-voluntary) control (e.g. iris of eye)
Tone
- Maintained in partial state of contraction
- No true RMP (-20 to -65mV), higher if active, lower if inhibited
Force generation
- Despite 20% less myosin and 100 fold less ATP useage…
- Can generate as much tension as skeletal m. per cross-section
- Contractions are much slower
Plasticity
- If stretched, initially tension increases
- After time it relaxes and tension falls (possibly even below initial)
(e.g. the bladder wall w/ increased volume)
Contraction of unitary SMCs stimulated by:
1. Stretch muscle causes contraction in the absence of innervation (membrane potential spikes)
2. Cold increases activity
3. ACh decreases smooth muscle potential and increases spike frequency so resulting in more
active muscle
4. Adrenaline and noradrenaline increase smooth muscle potential and decrease spike frequency
causing decreased muscle activity
5. Neural
Synaptic and Junctional Transmission
Definitions and Facts
EPSP – excitatory post synaptic potential, begins 0.5ms, peaks 11.5ms, declines exponentially, due
to openings of Na+ or Ca2+ channels, not enough for generation of a full action potential, but can
summate
IPSP – the opposite, due to increased Cl- or opening K+ channels or closure Na+ or Ca2+ channels
Temporal summation – repeated EPSPs prior to decay
Spacial summation – if activity present at more than one synaptic knob
- the EPSP is not an “all-or-none” response, but a graded proportional response to the strength of
afferent stimulus
Occlusion – the sharing of post-synaptic neurons results in a decrease in expected response
Slow synaptic potentials – in autonomic ganglia, cardiac m. SMC, cortical neurons, latency 100500ms last several seconds, due to K+ conductance
2010-1, 2006-2
In the synapse where can inhibition occur
1. Post-synaptic (direct due to IPSP, or indirect due to previous post synaptic discharge)
- E.g. in the spinal cord the reflex contraction to the agonists at the same time caused inhibition of
the antagonists (reciprocal innervation via interposed inhibitory neuron)
2. Pre-synaptic
- Via neuron that ends on excitatory endings (axoaxonal synapse)
- By 3 mechanisms:
i. GABA ->  intracellular Cl- -> decreasing AP,  of Ca2+ and therefore transmitter release
ii. Voltage gated K+ channels -> also decreases Ca2+ entry
iii. Direct inhibition independent of Ca2+
Neuromuscluar transmission
Neuromuscular junction: endfeet containing vesicles with acetylcholine insert into junctional folds
on the motor endplate
AP -> increased permeability to Ca2+ -> triggers exocytosis of acetylcholine vesicles -> diffuses to
nicotinic receptors -> increased Na+ and K+ conductance -> depolarizing endplate potential
The acetylcholine then removed by acetylcholinesterase (high conc in NMJ)
Smooth and Cardiac muscle
- Multiple branches of noradrenergic (?cholinergic) are beaded with varicosities allowing 1
discharge to innervated many effector cells
- Synapse en passant: the neuron make synapses, then passes on to make more synapses –
supplying many muscle fibres
- EJPs: excitatory junctional potentials are seen by stimulation with the neurotransmitter
(noradrenaline or acetylcholine depending on tissue) as discrete potentials (like endplate
potentials) and can summate with repeated stimuli
- IJPs: the opposite, hyperpolarizing, seen in tissues inhibited by noradrenaline
Denervation hypersensitivity
- Increased sensitivity to acetylcholine after dennervation
- Skeletal m. atrophies also, SMCs don’t, but become hypersensitive to activating mediator
- Limited to the structures immediately innervated by destroyed neurons, i.e. supra segmental
spinal lesion doesn’t cause hypersensitivity to paralysed skeletal muscle
- Multiple causes: upregulation of receptors, and reduction in mediator reuptake