lecture 17

Question 1

Sodium and chloride are osmotically active, what does this mean?

Answer 1

• they will attract water

Question 2

Which direction does water move across a semi-permeable membrane?

Answer 2

• from the low solute concentration to the high solute concentration

Question 3

How can the osmotically driven movement of water be problematic?

Answer 3

for cells as it also exerts pressure

Question 4

Why do solute concentrations need to be carefully controlled?

Answer 4

• they contribute to factors such as membrane potentials and neuronal cell excitability

Question 5

Which sensors of osmolality are key for osmotic homeostasis?

Answer 5

• whilst there are peripheral sensors of osmolality, the central sensors that detect extracellular osmolality are key for osmotic homeostasis
• the main group are in the OVLT, but some other cell groups including those in the PVN and SON are osmosensitive too (though not understood why as they are behind the blood-brain barrier)

Question 6

What do OVLT neurons do in response to increased ECF osmolality? How?

Answer 6

• increase their action potential firing
• with increased ECF osmolality, water leaves the cell toward the area of higher solute concentration
• the cell shrinks
• this causes the conductance (the measure of whether membrane channels are open) to increase
• the opposite occurs with decreased extracellular osmolality

Question 7

What mediates the change in activity?

Answer 7

• the change in cell stretch

Question 8

To what is the change in conductance due?

Answer 8

• opening of a cation channel
• this allows sodium/calcium to enter the cell and depolarise it to threshold
• it fires action potentials

Question 9

What is the key channel that appears to mediate the firing of action potentials in the OVLT cells?

Answer 9

• a member of the transient receptor potential family – TRPV1

Question 10

How must TRPV1 be connected to the cellular skeleton?

Answer 10

• it must be connected to the cellular skeleton such that it is opened when the cell shrinks and closed when the cell swells

Question 11

Where do outputs from OVLT cells go?

Answer 11

• ACC: allows you to perceive that you are dehydrated –> thirst
• potentially a path to ACC via thalamus
• PVN
• SON
• these last two are critical for water retention: act via the kidney to remove water from the urine (i.e. save it from being excreted)
• these are the magnocellular cells in the hypothalamus that secrete vasopressin

Question 12

What are magnocellular cells?

Answer 12

• neurosecretory cells located in the hypothalamus whose axons travel down the pituitary stalk and whose ‘synapse’ is on a blood vessel
• make vasopressin
• package it in vesicles which stay in the pre-synaptic terminals to be released when the cell is excited
• make quite a lot
• release a hormone as their transmitter, and therefore need to release quite a lot
• vasopressin has a number of effects but in this context it is important for the maintenance of osmolality homeostasis
• vasopressin, aka ADH
• cell bodies in paraventricular nucleus
• axons travel down and around through superoptic nucleus to get to pituitary stalk

Question 13

What is the biochem of vasopressin?

Answer 13

• made with a signal peptide
• a large binding protein is made with it
• 9 amino acids - Gly in the 10 position (which is removed) is necessary for the amidation of the Gly residue in the 9 position of AVP (arginine vasopressin)

Question 14

What does vasopressin do when it gets to the kidney?

Answer 14

• interacts with its receptor: g-protein coupled receptor (metabotropic receptor)
• V1 and V2 receptor
• V2 is the important receptor in the kidney
• activation of adenyl cyclase produces cAMP
• this via a number of steps has two main effects:
  1. go to the nucleus and increase transcription of AQP2, increased synthesis, put into vesicles and inserted into the membrane
  2. promote insertion of AQP2 into the membrane

Question 15

What are aquaporins?

Answer 15

• pores in the membrane that allow greater movement of water across the membrane

Question 16

What is another consequence of dehydration?

Answer 16

• decreased blood volume leading to decreased blood pressure
• especially in cases of severe dehydration there can be a risk of blood not being able to adequately perfuse the body

Question 17

How do we counter-act this lowered blood pressure due blood volume loss?

Answer 17

• autonomic nervous system

Question 18

Where are the outputs of the PVN?

Answer 18

• posterior pituitary (vasopressin)
• long projections down to spinal cord and along the way some projections into VLM (ventral lateral medulla)
• VLM and its projections to the spinal cord as well as the PVN projections to the spinal cord are major regulators of sympathetic activity

Question 19

What is the effect of increasing renal sympathetic activity?

Answer 19

• Juxtaglomerula apparatus: retention of sodium
• tubule: retention of water
• renal blood flow
• all work together to maintain homeostasis

Question 20

What makes up the autonomic nervous system? (visceral motor system)

Answer 20

• sympathetic and parasympathetic diversion

-

Question 21

Where does the visceral motor system innervate?

Answer 21

• most of the viscera

- most of our internal organs/functions require ongoing activity from the visceral motor system

Question 22

What is the difference between the somatic motor system and the visceral motor system?

Answer 22

• somatic motor neurons have their cell bodies in the CNS and they directly synapse on their target skeletal muscle
• sympathetic and parasympathetic have preganglionic fibres and postganglionic fibres
• the autonomic nervous system consists of two neurons connected in series
• the neuron innervating the target occurs outside the CNS
• the preganglionic cell is short in sympathetic while ganglionic/post-ganglionic cell can travel quite some distance to reach its target
• opposite for parasympathetic: ganglia tend to be within/near the target tissue
• gives us an extra level of modulation

Question 23

Where in the spinal cord do we have the sympathetic system?

Answer 23

• sympathetic pre-ganglionic neurons exist in the thoracic and lumbar segments of the spinal cord
• visceral motor system likes to sit in the middle of the spinal cord in the intermediate grey zone (between dorsal and ventral horns), specifically in the intermediolateral cell column (specifically lateral horn, this horn is not in cervical)

Question 24

Where do sympathetic visceral motor neurons send their axons?

Answer 24

• out via the motor side i.e. ventral
• send axons to post ganglionic neurons in the sympathetic trunk: sympathetic chain ganglion
• synapse
• the ganglionic/postganglionic cell projects out to target
• or the pre-ganglionic fibre can go through the sympathetic ganglion and out through to the prevertebral ganglion (synapse) - tend to be in midline, usually to gut

Question 25

How is the parasympathetic nervous system organised?

Answer 25

- pre-ganglionic cell bodies are situated within the medulla and the pons (heart, lungs etc) and also sacral spinal cord (to bladder, penis, uterus etc) - viscerotopy - these cells then project out in long projections, a large number of which project out in the vagus nerve - neurons in the intermediate part of the sacral spinal cord, medial to the sympathetic neurons

Question 26

What are some different functions of the sympathetic vs parasympathetic divisions?

Answer 26

- some viscera receive only sympathetic innervation: liver (glucose production and release from liver), constriction of most blood vessels - blood vessels to erectile tissues are affected by the parasympathetic nervous system - some tissues receive information from both divisions of the visceral motor system - often the case is that innervation goes to different cells within that tissue - e.g. sympathetic activity dilates your pupils, parasympathetic constricts, go to different muscles around the eye - not innervating the same muscles to cause this pupil change, one goes to muscles that dilates and one that goes to muscles that constrict; pancreas - sometimes we get sympathetic and parasympathetic innervation to the same cell: e. g. heart: pacemaker neurons in the heart that regulate the speed at which your heart beats, sympathetic activity on these cells increases the rate of firing, therefore increasing heart rate, while parasympathetic decreases rate of firing of these cells

Question 27

What is a third division of the autonomic nervous system?

Answer 27

- the enteric nervous system of the gut

Question 28

How do transmitters differentiate different components of the visceral motor system as well?

Answer 28

- somatic motor system uses acetylcholine, with a nicotinic receptor that results in contraction of muscles (N1) - motor neurons of the parasympathetic and sympathetic divisions also use acetylcholine as their transmitter between pre-ganglionic fibres and the post-ganglionic fibre, also with a nicotinic receptor (N2) - the difference lies in the post-ganglionic fibre - post-ganglionic fibre of parasympathetic neurons also use acetylcholine as their transmitter but are greeted with muscarinic acetylcholine receptors (M) (metabotrobic) - sympathetic post ganglionic neurons make noradrenaline as their neurotransmitter - detected by alpha- and beta- adrenergic receptors - sympathetic fibres can also synapse on the adrenal medulla, which can be considered a sympathetic ganglion in a sense, receives an input from the preganglionic neuron and directly releases adrenaline into the blood stream as a result of stimulation

Question 29

How do symapathetic neurons affect blood vessels?

Answer 29

- symapathetic neurons have lots of release sites (varicosities) along the length of the blood vessel onto multiple different vascular smooth muscle cells - noradrenaline is released it goes across a 'synapse' to the smooth muscle cell to cause constriction - not a synapse in the way that we are used to

Question 30

How do we get noradrenaline and adrenaline?

Answer 30

metabolic pathway - tyrosine - DOPA (via tyrosine hydroxylase) - Dopamine (via L-Aromatic amino acid decarboxylase) - Noradrenaline (via dopamine-beta-hydroxylase) - Adrenaline (via phenylethanolamine-N-methyltransferase)

Question 31

What is cycling of noradrenaline and dopamine? How can this be affected?

Answer 31

- normally when a neuron releases NA or DA this activates presynaptic receptors which encourage the reuptake of the neurotransmitter back into the cell - cycling - many drugs of addiction such as cocaine or amphetamine block the receptors that allow the cycling of these chemicals of which the effect is to increase the concentration of the neurotransmitter in the synaptic region and in so doing to prolong its activity - mimic and increase the activity of the sympathetic nervous system - e.g. someone who takes cocaine will show increases in heart rate, vasodilation, dilated pupils because of the drugs effect on the sympathetic nervous system - probably the addictive quality is because of the effect on the release of dopamine