Lecture 25 Flashcards
What are the two types of contractions of the GI tract?
Tonic contractions
phasic contraction
What are phasic contractions?
This is when there is contractions and relaxations in seconds
What are tonic contractions?
These are sustained contractions that last minutes to hours
Where do phasic contractions occur?
oesophagus, gastric antrum (stomach), small intestine
Where do tonic contractions occur?
lower oesophageal sphinter, orad stomach (near mouth), ileocecal and internal anal sphincters
What are the two main stages in the motility patterns in the GI tract?
- fasting state
- fed state
What is the purpose of the fasting motility pattern?
- clearing undigested material and secretions
- regulating intestinal microflora
What is the purpose of the fed motility pattern?
- Storage
- Movement at a controlled rate
- Mixing
- Exposure to absorptive surfaces
What is the fasting motility complex called?
The migrating motor complex
Describe the migrating motor complex
This starts 4-5 hours post meal absorption and it is 2 hours in duration from the stomach to the end of the large intestine
What are the three phases of the MMC?
- intense
- inactive
- intermittent
What is the function of the MMC?
- clears undigested material and secretions
- regulates intestinal microflora
- epithelial cell turnover
Describe the hormonal regulation of the MMC?
hormonal - motilin released by intestinal M-cells (M-cells trigger sensory neurons which feed into the ENS and have an effect on the motor neurons)
neuronal - motilin stimulates both the ENS and autonomic NS
What are the three base motility patterns in the fed state?
- storage function
- peristalsis
- segmentation
Describe the storage function the fed state
This is mainly in the stomach and colon. It involves the relaxation of smooth muscle which allows the volume of luminal contents to increase without changes in pressure
Describe peristalsis function of the fed state
This is mainly in the lower oesophagus and stomach, small and large intestine. It is propulsive but also mixing as part of retropulsion in the stomach
Describe the segmentation function of the fed state
This is in the small and large intestine which is for mixing and exposure to absorptive surfaces
What are the two types of storage in the stomach?
- receptive relaxation
- accommodation
Describe receptive relaxation storage in the stomach
An event, (e.g. swallowing in the case of the stomach) triggers reduced muscle tone as content is moved along the tract (less resistance as content arrives). The relaxation of the stomach means that the pressure in the stomach is lower that in the oesophagus. This allows food to enter and not be pushed back.
Describe accommodation for storage in the stomach
This is progessive relaxation in response to a volume change
Describe peristalsis
This is when the ascending circular muscle contracts behind the bolus and the ascending circular muscle relaxes ahead of the bolus. The longitudinal muscle is shortening (contracting). It can also be combines with other motility patterns to produce complex patterns
Describe segmentation
This is when the circular muscle contracts in alternating segments. This is for mixing.
There is pinching and then a wave of peristalsis. The one inner circular layer is contracting rhythmically.
What is the major motility pattern in the small intestine?
Segmentation
The GI tract smooth muscles act as a what? What does this mean?
syncytium
This means that the cells contract together
What are the smooth muscles of the GI system interconnected with?
The are interconnected via gap junctions and adherens junctions
The muscle cells are arranged in ___________ with a ________ ________ in between them. Describe this
layers
neural plexus
There is the circular (inner) and longitudinal (outer) intestinal smooth muscle sandwiching neural components of the myenteric plexus
What is the dimension of the intestinal smooth muscle cells?
5 – 20 μM diameter and ~ 500 μM long
Individual muscle cells interact with how many other cells? How do they do this?
Around 10 surrounding cells via gap junctions and adherens junctions
Intestinal smooth muscle contain _______ and _______ filaments in an _________ arrangement (rather than being _______ like in skeletal muscle cells)
actin and myosin
irregular
striated
Is there troponin and tropomyosin in intestinal smooth muscle?
no, but there is actin and myosin
Why is there no troponin and tropomyosin in the intestinal smooth muscle?
Because instead there is calmodulin and MLCK.
After an action potential and depolarisation, there is entry of Ca2+ via the opening of Ca2+ channels. Ca2+ comes in and binds to calmodulin making a Ca2+-calmodulin complex. This activates the MLCKinase which phosphorylates the MLC. This interacts with actin to lead to contraction
How can we reverse the phosphorylation of MLC?
This is through MLCPhosphorylase enzyme. NO activates MLCP to get relaxation
The membrane potential of intestinal smooth muscle fluctuates ________
cyclically
The intestinal smooth muscle cells receive action potentials on a regular basis by which cells?
Interstitial cells of Cajal
Is the membrane potential of intestinal smooth muscle stable?
No, it varies between -40mV and -80mV
The membrane potential of intestinal smooth muscle fluctuates in a pattern of ______ ______ or ________ _________ _______. This is generated by which cells?
slow waves
basic electrical rhythm
interstitial cells of Cajal
The interstitial cells of Cajal spontaneously __________ and then __________ in a regular pattern. Because they are electrically connected to the smooth muscle cells, they will bring the smooth muscle cells to ________ and generate an ________ _______
depolarise
repolarise
threshold
action potential
Because of the effect of the interstitial cells of Cajal, the membrane potential of the smooth muscle cells isn’t ________; it fluctuates between these inputs. This means there is a period of time every cycle where they are very likely to reach __________ and the longer they reach threshold during that cycle of _________ the longer they are going to _______
stable
threshold
depolarisation
contract
The interstitial cells of Cajal generate ______ waves
slow
How do the interstitial cells of Cajal generate slow waves?
Through rhythmic changes in the activity of Na+/K+ ATPase and membrane K+ conductance
Where are the ICoC located?
- in the stomach and small intestine: in the smooth muscle layer next to the myenteric plexus
- in the colon: closer to the submucosa (boundary of muscle layer and submucosa)
Describe the arrangement of the ICoC
They are highly branched cells that send multiple branching processes to surrounding smooth muscle cells. They are electrically linked to other ICC and muscle cells by gap junctions
What do slow waves ALWAYS determine?
The frequency of contraction
There is a clear relationship between the slow waves and the what?
generation of a contraction
The frequency of slow waves is a property of what?
The ICoC in each region
Where is the frequency of slow waves faster and then is it slower? Give examples
It is faster in the proximal regions of the GI tract (digestion) eg. the duodenum has 12-20 per minute.
It is slower in the distal regions of the GI tract (absorption) eg. the colon only has 6-8 per minute
Action potentials are generates by ICoC which sets the ______. What determines how long the cells are above threshold?
Frequency
Other inputs
Although the frequency of contraction can be different between two different regions, does the frequency ever change within one region?
no
What do action potentials determine?
The force (size/amplitude) of contraction
The ______ _______ that are generated by the _______ will set the _______ and then other _________ are going to determine exactly how long the cells are above _________. So if you don’t have any other inputs, and you have just got a small signal from the ________, then those muscle cells will be at ___________ for a very short period of time, _______ and _________ will be interacting for a very short period of time and you will get a small __________. If you have some other input that further pushes that __________ and makes it last longer, you are going to have action potentials lasting in those muscle cells for much longer, and you are going to have a much ________ force of ________. You have pacemakers that bring the muscle cells to threshold periodically, and other inputs can make the threshold last longer or shorter to get a bigger or smaller force of contraction, but it won’t have an effect on the ___________.
action potentials ICoC frequency inputs threshold ICoC threshold actin myosin contraction depolarisation stronger contraction frequency
You can have very small contractions if what two things happen?
The membrane doesn’t reach threshold or not for very long
More action potentials or spending a longer period above threshold means what?
There is a bigger force of contraction
As well as more action potentials or spending a longer period above threshold resulting in a bigger force of contraction, you can also have inputs that influence the amount of Ca2+ that gets released with each action potential. What is this doing?
This is potentiating the action potentials.
Elevated Ca2+ results in more activated Ca2+-calmodulin complex and more activity in the Myosin Light Chain Kinase
What are two ways we can get a bigger strength of contraction?
- we can depolarise the cell membranes for longer
- a hormone or neurotransmitter can bind to a Gαq receptor
Explain how depolarising the cell membranes for loner results in a bigger strength of contraction
The longer they are depolarised, the more Na+ and Ca2+ channels are going to be opening and the more Ca2+ can come in.
You are also going to get voltage gated Ca2+ in the sarcolemma being opened and you’re going to get a Ca2+ on Ca2+ release effect.
Describe the first mechanism for regulating smooth muscle contraction
You depolarise the cell membrane and you open voltage gated channels (Ca2+ and Na+). This is going to result in an influx of Ca2+ (the Na+ will also depolarise the cell further). This will result in more Ca2+ being released, especially by ryanodine and you will get this Ca2+ induced Ca2+ release that will then allow the Ca2+ to interact with the calmodulin more and longer and result in a bigger contraction.
Explain how the binding of a hormone or neurotransmitter to a Gαq receptor can increase the strength of contraction
The Gαq receptor has 2 parts to its pathway:
- there is an IP3 molecule that is going to open IP3 gated Ca2+ channels in the SR and this is going to form another mechanism for the release of Ca2+
- there is receptor activation of PLC and production of IP3 which induces the release of Ca2+ via IP3 gated channels in the SR. This is also going to be more Ca2+ that can bind to calmodulin and more MLCK activated and stronger contractions.
Do the mechanisms for increasing the strength of contraction interact?
What is there potential for?
Yes and there is potential for potentiation.
This is when (eg.) there is a receptor that leads to more depolarisation and Ca2+ induced Ca2+ release and that the same time, you might have a hormone input that sets of the Gαq pathway that generates IP3 so you get IP3 specific Ca2+ release and that is going to be a really big contraction.
How can we down-regulate contractions? (3)
- hyperpolarisation of smooth muscle cells means you take the cells further away from threshold and the duration of the action potentials when you get the signals from the ICoC will be smaller
- you can increase the activity of the Myosin Light Chain Phosphatase which is going to take the phosphate off the myosin and result in relaxation
- you can also inhibit the excitatory neurons in the ENS
Slow waves pass a threshold and initiate action potentials. True or False?
True
The intestinal smooth muscles are triggered on a regular basis in a slow wave pattern by pacemaker cells called ICoC which are capable of spontaneous depolarisation and repolarisation. True or False?
True
Hormones and neurotransmitters can regulate contractions by
(a) modulating magnitude/strength of contraction OR
(b) affecting the frequency of contraction
They modulate the magnitude/strength of contraction only - they have little effect on frequency because this is determined by ICoC and varies by region
The signals and inputs that are going to determine the force of contraction is what?
Things in the lumen and these are detected by chemo-, osmo- and mechanoreceptors which will send messages via the ENS or hormones which will act on the GI smooth muscle to increase or decrease APs and therefore increase or decrease the force of contraction (the frequency doesn’t change).
Can the CNS have a regulatory effect on the GI smooth muscle?
yes, through the ANS
This is done in relation to emotional states or the presence or absence of food like smelling it and it will act through the sympathetic or parasympathetic pathways
What happens when you are super relaxed and you are eating food. What does the CNS do?
The CNS detects this and send a signal through the parasympathetic pathway to increase activity and it will release ACh and this will be detected by muscarinic cholinergic receptors in the ENS.
The ENS will then send excitatory signals via receptors on the smooth muscle to increase the duration that they are above threshold and therefore increase the force of contraction and stimulate motility to assist with digestion.
What happens when you are super stressed and eating? What does the CNS do?
When stress gets detected by the CNS, it will activate the sympathetic pathway which will produce adrenaline which acts on α adrenergic receptors in the ENS. The ENS will then send inhibitory signals to the GI tract smooth muscle which will result in that muscle being above threshold for less time and a lower force of contraction and it will increase the time it takes to digest food.
What is the effect of opioids on the GI tract?
They bind to opioid receptors (GαI receptor) in the myenteric plexus which is going to inhibit ENS neurotransmission. This is one example of inhibiting and excitatory message that would normally tell your smooth muscle to contract to aid in digestion.
When this happens, the ENS can’t send a message to the smooth muscle and the smooth muscle is not going to aid in digestion and absorption of luminal content and you slow down progress of chyme in the tract.
Why are opioids good when you have diarrhoea?
Because they slow down the progression of chyme and so you have more time to reabsorb any water and salt that is being lost to excess secretion.
How did Elvis die?
He had constipation and an enlarged colon which can cause damage to stretch receptors that initiate defecation.
His opioid use had inhibited his myenteric plexus - it is reduced his GI contraction and resulted in constipation.
Over time, because he had more content in his colon meant that he had an enlarged colon and that means that he needed more content to trigger the stretch receptors to generate defecation and he was having to do the Valsalva manoeuvre which increases the intrathoracic pressure which put pressure on the aorta and so everything in the aorta is pushed backwards (when your aortic pressure is higher than your ventricular pressure, the openings to the coronary arteries are open and the CA are filled and if you have any clots or anything else that can cause blockage of those coronary arteries, and you perform the manoeuvre and they get pushed backwards, you have a heart attack).
Which of the following statements about the spontaneous contractions of intestinal smooth muscle is not correct?
A. These are phasic contractions generated by interstitial cells of Cajal.
B. Spread of spontaneous contractions depends on gap junctions between intestinal smooth muscle cells.
C. The frequency of contractions is dependent on the region of the intestine.
D. Spontaneous contractions are generated by the parasympathetic nervous system.
E. Intestinal smooth muscle can contract independently of the central nervous system.
D. Spontaneous contractions are generated by the parasympathetic nervous system.
