Neural Function in Disease Flashcards
law of dynamic polarisation
there is a preferred cell-to-cell direction in which currents move
soma
cell body
Dendrite
collects signals from other neurons
Node of Ranvier
exposed axon that allows ions to diffuse in and out of the neuron
myelin sheath
insulation that speeds up transmission
Astrocytes
fills spaces between neurons in brain and most numerous cell in organ, mop up chemical messengers that accidently diffuse into intercellular space to stop signal going to wrong cells
how can ions move across a membrane
through pumps (active) or channels (passive)
where are K+ and negatively charged proteins concentrated?
cytoplasm
where are Na+, Cl- and Ca2+ concentrated?
the ECF (extracellular fluid)
at rest, state of potassium and sodium channels?
- At rest, leak potassium channels are open (not voltage dependant) and respond to pH, oxygen potential and mechanical stretch
- At rest, sodium channels are closed
resting potential of cell
-65mv due to large negative proteins that can’t diffuse out of cell
action potentials
short pulses of electricity fired when a neurone is stimulated, they are propagated along its length carrying information
process of generating an action potential
Sodium channels and voltage gated potassium channels are closed
Sodium channels open (depolarisation)
Sodium channel inactivate and voltage gated potassium channels open (repolarisation)
Voltage-gates potassium channels gradually close (hyperpolarisation)
what does a sequence of APs show?
long stimulus
After-hyperpolarisation
when the K+ tries to reach its own equilibrium potential of -80mV after repolarisation, so membrane potential undershoots before K+ VGICs can close
Depolarisation
change in polarity in the membrane potential of a cell
mechanism of voltage gated ion channels
- Na+ VGIC are closed at rest to maintain the resting potential
- A stimulus depolarising the membrane to -40mV distorts the protein to open it specifically to Na+ ions
- This rapidly causes much faster depolarisation for 1ms
- The channel inactivates by covering the pore and then closes when the protein returns to its resting configuration after repolarisation of the membrane, the physical pore power is removed
why K+ VGIC are much slower to reopen after depolarisation ?
entry of K+ resets the membrane potential to resting, during the refractory period after an AP the cell cannon generate another AP so that depolarisations are discrete.
propagation in unmyelinated neurones
In unmyelinated neurones, depolarisation at one point of the membrane (production of an AP) sets up local circuits, so depolarisation continues as a wave down the length of the neurone
salutatory conduction in myelinated neurones
Between myelin, there are gaps called Nodes of Ranvier where there is a high density of ion channels. APs are initiated in an axon hillock (part of cell body of a neurone that connects to the axon) and jump from one node to the next
factors that increase conduction velocity
Myelin, increased axon diameter and higher temperatures
Mechanoreceptors
unmyelinated fibres in the skin sensitive to stretch/bend/pressure
Mechanosensitive ion channels
gates opened by stretching of membrane
dermatome
the area of skin with innervation supplied by one nerve
stimulus detected by free nerve endings
Pain, temperature, crude touch
stimulus detected by pacinian corpuscles
Deep pressure, vibrations
synapses
gaps between neurones
neurotransmitter
endogenous chemical messenger that conveys neuronal information from a pre-synaptic terminal to its post synaptic target
neurotransmission process- where are enzymes for the synthesis of NTs produced?
neurone cell body and move down the axon on microtubules
neurotransmission process- what are NTs produced from?
precursors in the pre-synaptic terminal which is then stored in vesicles
neurotransmission process after action potential reaches the pre synaptic terminal
- When an action potential reached the terminal, the membrane is depolarised which causes voltage gated calcium channels to open
- Ca2+ makes the NT vesicles fuse with the membrane (calcium sensing)
- The NT is released into the synaptic cleft (exocytosis)
- It binds to receptors on the post synaptic neurone
- Enzymes break down the NT and its constituents are taken up into the pre-synaptic terminal for re-use
- A new empty vesicle is pinched off the membrane into the pre-synaptic terminal (endocytosis)
- This is filled with NP (loading) for the next AP
Ionotropic receptors
fast ligand-gated ion channels that open when the NT binds
Metabotropic receptors
slow because they activate a second messenger system (via GPCRs)
molecules that increase excitability of the post-synaptic neurone
acetylcholine, noradrenaline and glutamate
molecules that decrease excitability of the post-synaptic neurone
GABA and glycine
integration of signals allows
EPSPs to add up and if the threshold potential is met, generate an AP
production of EPSPs
At an excitatory synapse, if sufficient NT binds to NA+ ionotropic receptors the membrane will depolarise to produce an excitatory post-synaptic potential (EPSP)
production of IPSPs
occur at inhibitory synapses because Cl- channels are opened instead, further polarising the membrane (making it more negative instead of reversing the voltage, so it is harder to generate an action potential)
Spatial summation
when a neurone combines multiple EPSPs from different synapse connections
Temporal summation
when a neurone combines multiple consecutive EPSPs from the same synapse
Nicotinic receptors
ionotropic receptors that respond to acetylcholine (Ach), are agonised by nicotine and antagonised by curare
Muscarinic receptors
metabotropic Ach receptors, are agonised by muscarine and antagonised by atropine
GABA inhibitory receptors
agonised by ethanol and other depressants that reduce stimulation
Somatic motor fibre
one nerve fibre that connects CNS to the skeletal muscle it innervates
relationship of axial and distal muscle neurones
- Axial muscle neurones are medal to those of distal muscles
relationship of flexor and extensor muscle neurones
- Flexor muscle neurones are dorsal to extensor muscle neurones
The motor end plate
pre-synaptic terminal for one skeletal muscle fibre. Many motor end plates split off from one nerve so that it can innervate the whole muscle and coordinate its contraction
Motor unit
alpha motor neurone form the spine and fibres of the muscle that it innervates (causes to contract) which then splits into many synapses (motor end plates)
Motor neurone pool
set of alpha motor neurones that innervate one muscle, so damage to a single motor unit will not prevent normal muscle activity
what does the autonomic nervous system do?
controls involuntary reactions and innervates smooth muscle, cardiac muscle and gland cells
where are the cell bodies of ANS neurones?
cluster in ganglia which run down beside the spinal cord
Components of the autonomic nervous system
sympathetic and parasympathetic nervous systems
adrenaline pathway
- Pre-ganglionic neurones release Ach and post-ganglionic release noradrenaline (NA) so receptors in the ANS are known as adrenoreceptors
Ach pathway
- All neurones in this system release Ach and neurones travel long distances to target organs since most original in the cranial (neck) spinal cord
Contraction of muscles leads to
shortening of muscle fibres
areas where smooth muscle is present
in blood vessel wall and the digestive tract lining
Neuromuscular junction-
synapse between the neurone and the muscle fibre
action of acetylcholine to imitate contraction and degradation
Ach crosses NMJ and stimulates receptors to initiate contraction then is degraded by acetylcholinesterase enzymes so that acetic acid and choline (products) diffuse back to the pre-synaptic neurone to be resynthesized into Ach.
muscle contraction- movement of myosin and actin
- The EPSP generated in the post-synaptic membrane (sarcolemma) travels through T-tubules (transverse tubules) into the fibre
- This causes Ca2+ of the sarcoplasmic reticulum to open up
- Ca2+ diffuses into the sarcoplasm and binds to troponin C so that the myosin heads are free to attach to binding sites on the actin filament
- This binding causes a conformation change in the heads which pivot and slide the actin filament along the myosin filament to shorten the sarcomere
- ATP is hydrolysed so the head detaches and swings back into its original position, ready to repeat the process for as long as APs and Ca2+ are present
Reflex
involuntary movement in response to a stimulus, instead of being processed by the brain and producing a conscious response, they travel through a reflex arc as far as the spinal cord and back
Myotatic reflex
in antagonist pairs of muscles, they are innervated so that one is inhibited when the other is excited to allow movement eg. in knee reflex jerk so that extensors contract, flexors relax
Cross extensor reflex
one leg extends when one flexes so gives stability when one leg is moved from pain
Vestibulo-ocular reflex
when the head is rotated, extraocular muscles (around the eyes) are inhibited on one side and excited on the other to fix the position of eyes- line of sight
hyponatremia
Less Na+ so less excitability, can be caused by diuretics cirrhosis ect., symptoms= cramps, fatigue, weakness
hypernatremia
More Na+ so more excitability, causes: water loss, renal failure ect. symptoms: Tremor, seizures, hyper-reflexia, thirst
hypokalaemia
Less K+ so less excitability Causes: Diuretics, cirrhosis, renal disease, malnutrition, malabsorption in GI tract,
Symptoms: Mild: weakness, fatigue, constipation, arrhythmias
Sever: paralysis of muscles including vital systems
hyperkalaemia
Less K+ so less excitability
causes: drug interactions with kidney function, symptoms: Impaired vital organ systems
channelopathies
diseases which affect ion channels (eg. mutations) and thus depolarisation/repolarisation of cells
demyelinating diseases examples
damage the Schwann cell insulation of neurones so lower AP conduction eg. multiple sclerosis, Guillain Barre syndrome (autoimmune)
myasthenia gravis
the immune system attacks Ach receptors so signals can’t be sent at the neuromuscular junction leading to weakness and fatigue
