neuro physiology Flashcards
Skeletal Muscle Contraction
What is the sequence of events in the contraction of a skeletal muscle fibre,
starting at the motor end plate?
● Discharge of a motor neuron
● Release of preformed acetylcholine at the motor endplate via exocytosis
● Diffusion of Ach across the synaptic cleft
● Binding of Ach to postsynaptic nicotinic Ach receptors
● Increase Na and K conductance in the end plate membrane
● Generation of the end plate potential
● Generation of action potential in muscle fibres
● Inward spread of depolarisation along the T tubules
● Release of Ca from terminal cisterns of the sarcoplasmic reticulum and diffusion
to thick and thin filaments
● Binding of calcium to troponin C, uncovering myosin binding sites on actin
● Formation of cross linkages between actin and myosin and sliding of thin on thick
filaments, producing movement
What is the sequence of events in relaxation of a skeletal muscle fibre
● Calcium is pumped back into the sarcoplasmic reticulum
● Release of calcium from troponin
● Cessation of interaction between actin and myosin
How does a tetanic contraction occur?
● The contractile mechanism has no refractory period
● Repeated stimulation before relaxation has occurred leads to a summation of
contractions fast repeated stimulation causes a fused continuous tetanic
contraction which can be complete or incomplete
Smooth Muscle Contraction
Describe the sequence of events in contraction and relaxation of visceral smooth
muscle
● Binding of Ach to muscarinic receptors
● Increased influx of calcium into the cell
● Activation of calmodulin – dependent myosin light chain kinase
● Phosphorylation of myosin
● Increased myosin ATPase activity and binding of myosin to actin
● Contraction
● Dephosphorylation of myosin light chain phosphatase
● Relaxation or sustained contraction
What factors influence intestinal smooth muscle contraction?
● Stretch of smooth muscle causes contraction in the absence of innervation
● Cold increases the activity
● Ach decreases smooth muscle potential and increases spike frequency resulting
in more active muscle
● Adrenaline and noradrenaline increase smooth muscle potential and decrease
spike frequency causing decreased muscle activity
● Neural mechanisms
Cholinergic transmission
Please describe the synthesis, release and action of acetylcholine at the nerve
synapse
● Choline is synthesised in neurons and actively taken into cholinergic neuron
● Acetyl CoA and choline are used to form acetylcholine via choline
acetyltransferase
● This is packaged in synaptic vesicles via transporter
● When the nerve is stimulated, the vesicles execytose the Ach into the synaptic
cleft, where it binds the postsynaptic Ach receptor
Once released into the synaptic cleft, how is its effect terminated?
● Diffusion
● Catabolism by pseudocholinesterase in the circulation
● Acetylcholinesterase on the postsynaptic membrane
● Reuptake of choline into the presynaptic nerve terminal
Describe the differences between the two different types of acetylcholine
receptors
● Divided into nicotinic and muscarinic
● Muscarinic – actions mimicked by muscarine and blocked by atropine. Found in
smooth muscle, glands and brain. G protein coupled receptors.
● Nicotinic – actions mimicked by nicotine, found in the NMJ, autonomic ganglia
and the central nervous system. They are ligand gated sodium ion channels.
Adrenergic transmission
Which catecholamines act as neurotransmitters?
● Noradrenaline
● Adrenaline
● Dopamine
Outline the biosynthesis of adrenaline
● Starts with tyrosine, converted to DOPA via tyrosine hydroxylase
● DOPA is converted to dopamine byb dopa decarboxylase
● Dopamine to noradrenaline by dopamine hydroxylase
● Norad to adrenaline via phenylethanolamine methyltransferase
Describe the sequence of events at the noradrenergic synapse, following
stimulation of a sympathetic nerve
● Noradrenaline is stored in granulated vesicles in the nerve
● Released into the synaptic cleft by exocytosis once is is stimulated
● Acts on postsynaptic receptors
● Action is terminated in 2 ways:
○ Reuptake to the presynaptic neuron then metabolised by MAO to inactive
derivatives
○ Catabolised in the synaptic cleft by COMT
Nerve action potential
Define resting membrane potential of a neuron
● The potential difference across a cell at rest, as a result of separation of positive
and negative electrical charges across a cell membrane.
● Inside is negative relative to outside.
● The normal RMP is -70mV in a neuron.
How is the resting membrane potential generated?
● Main ions involved are K and Na
● The Na/K ATPase creates an electrochemical gradient by pumping out 3 Na for
every 2 K in
● Na and K diffuse down their concentration gradient across a semipermeable
membrane (K wants to go out, Na wants to come in)
● The cell membrane is more permeable to K at rest – which is why the RMP is
close to the equilibrium potential for K
Why is a cell more excitable in hyperkalaemia?
RMP moves closer to the threshold potential for eliciting an action potential (it becomes
less negative on the inside of the cell)
Please draw a nerve action potential and indicate the sequence of events that
occur
Key Points you must include:
● Starts at -70mV
● After a depolarising stimulus occurs, voltage gated Na channels become active
and Na enters the cell
● When the threshold potential is reached (-55mV) , the voltage gated Na channels
overwhelm the K channels
● Entry of Na causes opening of more voltage gated Na channels and further
depolarisation in a positive feedback loop, causing the upstroke of the action
potential (peaks at +35mV)
● Voltage gated Na channels enter an inactivated state for a few milliseconds
before returning to the resting state, this inhibits further Na movement
● The reversal of membrane potential causes opening of voltage gated K channels,
resulting in repolarisation via K efflux and the end of the AP
● Slow return of K channels causes hyperpolarisation (below -70mV)
● Over time this is corrected and the cell returns to resting membrane potential
Nerve Conduction
Where are ion channels distributed in myelinated neurons?
Concentrated in the nodes of ranvier, Na channels are flanked by K channels
What factors affect conduction?
● Myelinated is quicker than demyelinated
● Size
● Direction of conduction
In the synapse, where can inhibition occur?
● Post synaptic – via direct or indirect inhibition (i.e. refractory periods or after
hyperpolarisations)
● Pre-synaptic – mediated by neurons that end on excitatory endings (axo-axonal
synapses)