Sanders. Upper and lower GI motility Flashcards
The motility patterns of gastrointestinal organs are due to contractions of (blank) in the walls of the organs
smooth muscles
(blank) are Regions such as sphincters and the fundus of the stomach produce sustained (tonic) contractions or periods of sustained relaxation.
tonic contractions
(blank) are – Other regions, such as the distal stomach or small intestine, produce contractions that are transient with periods of relaxation between contractions.
phasic contractions
(blank) are Phasic contractions superimposed upon tonic contractions. In many cases enhanced phasic contractions elicited by agonists are superimposed upon a sustained increase in basal tone.
mixed contractions
(blank) are what allow GI smooth muscles to often be spontaneously active in the absence of exogenous stimuli
myogenic mechanisms
(blank) regulation is when Motor neurons (both excitatory and inhibitory) innervate smooth muscle tissues and regulate the force and pattern of smooth muscle contractions.
neural regulation
THis is why Many circulating agents affect the contractility of GI smooth muscles.
hormonal activation
What kind of regulation is this?
Many substance produced in the immediate environment of GI smooth muscle cells affect contractility.
humoral or paracrine
What is the basic mechanism of movement?
myogenic
What provide direction to muscle?
neural regulation
(blank) contain myosin and actin with dense bodies
smooth muscle cells
(boank) are flask shaped invaginations in the Plasma membrane. They are arranged in rows interposed between dense bodies. They are close to cisterna and tubules of the SR. And it has The plasmalemmal Ca-pump ATPase, the transport protein that extrudes calcium from the cell and helps maintain homeostasis within it.
caveoli
SM cells are connected via (blank)
gap junctions
The most important gap junction protein in SM cells is (blank)
connexon 43
Ions can move from cell-to-cell
through . Thus, they produce low electrical
resistance pathways between cells. Allow for electrical and chemical coupling between cells.
gap junctions
What mmakes up a gap junction?
hexameric assembly of GJ proteins
There is no troponin in smooth muscle so instead we have (blank) which binds the calcium and it activates (blank) which then activates the myosin light chain in SM> it phosphorylates this myosin light chain which activates cross bridge formation which allows for the shortening of the myosin head which pulls the actin by it and ATP displaces the ADP which makes the muscle contraction. This process stops when myosin is dephosphorylated. SM have a very slow contraction in comparison to other muscles.
calmodulin
myosin light chain kinase
What controls contract of smooth muscle?
phosphorylation! phosphate=conrtaction dephosphorylate=relaxation
Kinase (phosphorylate)
phosphatase (dephosphorylate)
How do you get the calcium within a cell to start a contraction?
via voltage dependent Ca channels and nonselective cation channels
Many (blank) are expressed in GI SM cells
G protein coupled receptors
Calcium can alter be released from intracellular stores when activated; how?
Ca channels in the SR activated by IP3 receptors
(blank) increases the effectiveness of Ca2+ in contractions
Ca2+ sensitization pathway
What are the two major enzymes involved in Calcium sensitization?
Protein kinase C (PKC)
Rho Kinase
What does this describe:
These mechanisms decrease the activity of myosin light chain phosphatase (MLCP), maintaining MLC20 phsophorylation and contraction.
calcium sensitization
What do you want to inhibit to get a contraction?
you want to inhibit MLCP
Mechanisms for Ca2+ desensitization are activated by (blank)
inhibitory agonists
How do you increase the activity of MLCP and therefore decrease contraction and lessen Ca2+ sensitization.
Activation of AC -> cAMP-> activation of protein kinase A
Phosphorylations by this enzyme increase the activity of MLCP.
Inhibitory agonists also affect (blank)
excitation-contraction coupling
Give an example of how inhibitory agonists affect excitation-contraction coupling.
Protein kinase G and A activate K+ channels. Increase in K+ causes hyperpolarization and decreases opening of voltage dependent calcium channels. This reduces Ca2+ entry and reduces contraction.
What are the major excitatory receptors in the GI smooth muscle?
Muscarinic receptors (M2 & M3) Neurokinin receptors (NK1 & NK2)
What are the major inhibitory receptors in the GI smooth muscle?
Soluble guanylate cyclase (not a membrane receptor) Purine receptors (P2Y1) Peptide receptor (VIP1)
What are the major excitatory hormone receptors in the GI smooth muscle?
Gastrin receptors
Cholecystokinin (CCK) receptors
Motilin
What are the major inhibitory hormone receptors in the GI SM?
secretin receptors
What are the major receptors for paracrine substances in GI SM?
Prostaglandin receptors
Histamine receptors
protease-activated receptors (PAR)
Serotonin (5-HT) receptors
The behavior of (blank) cells is affected by inputs from motor neurons and by electrical connections (gap junctions) with interstitial cells and more.
smooth muscle
1SMC + xSMCs=?
smooth muscle tissue (interactions via electrical and mechanical connections)
xSMCs + ICs =?
integrated SIP syncytium (interactions via electrical connections)
xSMCs + ICs + motor neurons =?
controlled smooth muscle tissue (interactions via neurotransmitters)
xSMCs + ICs + motor neurons + hormones + paracrine substances = ?
controlled smooth muscle tissue (interaction via circulating and local chemicals)
xSMCs + ICs + motor neurons + hormones + paracrine substances + inflammatory mediators = ?
pathological smooth muscle tissue
SMooth muscle cells are excitable. THey express a variety of (Blank) in the PM and organellar membranes that set and regulate what three things?
transport proteins
1) set and regulate membrane potential
2) generate excitable events
3) facilitate calcium entry into and removal from cytoplasm
How does Cl- move with a cell?
HOw does K+ move with a cell?
Cl- channels, while mediating outward movement of Cl- ions in most instances, still generate net inward current (defined as the inward flux of positive charge).
Many species of K+ channels are present and these channels produce outward currents due to the ionic gradients of smooth muscle cells.
What makes the plasma membrane negative?
Greater resting permeability of K+ channels makes the plasma membrane negative
Two types of Ca2+ channels are responsible for releasing Ca2+ from internal stores in sarcoplasmic reticulum. What are they?
These are IP3 receptor-operated channels (IP3) and ryanodine-sensitive (RYR) channels
Several exchangers and pumps help to maintain gradients. The (blank) helps remove Na+ that leaks into cells and exchanges 3 Na+ for 2 K+ ions. The plasma membrane (blank) removes Ca2+ that enters cells during excitable events. A (blank) retrieves Ca2+ into Ca2+ stores. Energy from ATP is used for these ATPases to pump the ions up electro-chemical gradients. The (blank) removes Ca2+ from cells and utilizes the downward gradient of Na+ for this task.
Na+/K+ ATPase (“Na+ pump”)
Ca2+ ATPase
sarcoplasmic reticulum Ca2+ ATPase (SERCA) Na+/Ca2+ exchanger (NCX)
How is resting membrane potential set in GI smooth muscle cells?
In GI muscle cells resting membrane potentials are typically between (blank)
Ionic gradients to sustain resting potentials are maintained by ion pumps using (blank) for energy.
permeability of PM to ions especially K+ channels\ -50 and -80 mV
ATP
What does the AP look like in the gastric antrum?
single peaks equally spaced
What does the AP look like in small intestine?
2-3 superimposed spikes followed by brief moments of recovery
What does the AP look like in colon?
numerous superimposed spikes followed by brief moments of recovery
(blank) increases open probability of Ca2+ channels
slow wave depolarization
What do Interstitial cells of Cajal (ICC) do?
generate constant slow wave activity in phasic regions of the gastrointestinal tract. (which increase prob of open Ca2+ channels)
Inward current or suppression of outward current=?
Outward current=?
depolarization=big contraction
hyperpolarization= tiny contraction
Do all parts of the GI tract have the same frequency of electrical activity?
no
What generate the pacemaker activities of the GI tract and form networks throughout GI tract?
ICC
What are the 3 types of ICC and where do you find them?
ICC-MY next to myenteric plexus
ICC-IM in muscle bundles (near processes of enteric neurons)
ICC-SEP in septa of SM cell bundles
The response at the motor neuron is not just a muscle response it is also a response to the (blank) within it.
Interstitial cells
Which ICC are primary pacemaker (i.e generate slow wave)?
ICC-MY