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GI part 2 > Regulation of GI Fuction (muscle) > Flashcards

Regulation of GI Fuction (muscle) Flashcards

1
Q

smooth muscle characteristics

A

Multi-unit and Single-unit Smooth Muscle
Slow Wave Potentials and Action Potentials
Excitation-Contraction Coupling

arranged in thick and thin filaments
relatively small, unstriated
actin and myosin present, no sarcomeres, no z lines
Dense Bodies Present

No troponin
       -Calmodulin, caldesmon and calponin
       -Tropomyosin does not block 
  binding sites
-Cross bridges: myosin activation via
 Ca2+-dependent phosphorylation of
  regulatory light chains                  
No T tubules
-Caveolae
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2
Q

Smooth muscle innervation

A

both para and sympathetic nervous system

Multiple contacts between neuron and smooth muscle cell-No true NMJ
Varicosities: axon swelling at each contact point; contain neurotransmitters
Relatively little specialization of postsynaptic membrane
Receptors are more widely dispersed

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3
Q

2 types of smooth muscle

A

multiunit smooth

single-unit smooth (visceral smooth, unitary smooth). Gap junctions permit coordinated contraction

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4
Q

multi-unit smooth muscle

A

neurogenic stimulation (recruitment like skeletal m.), densely innervated, contraction is controlled by neural input or hormones. Autonomic efferents.

Contract as separate motor units (little or no electrical coupling between cells), fine motor control possible

Examples; ciliary body, iris, piloerector m.m., some blood vessels, vas deferens

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5
Q

single-unit (unitary, visceral)

A

Myogenic (specialized cells may exhibit “pacemaker” activity. Oscillation of membrane potential: slow wave

Cells contract as a single unit (electrical syncytium - gap junctions), coordinated contraction, degree of coupling may vary

Examples: gastrointestinal tract, uterus, ureter, bladder, some blood vessels.

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6
Q

graded potentials in smooth muscle

A

(not quite action potentials)
Hyperpolarizing or depolarizing
Spatial or temporal summation
Stimuli: mechanical, humoral, neural

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7
Q

slow-wave potentials

A

G.I. pacemaker cells: initiate spontaneous electrical activity
-Interstitial cells of Cajal
-Between longitudinal & circular m.m. of the muscluaris externa layer
Repetitive oscillation in Vm = Slow-wave potential
-Generally thought to result from cyclic opening of Ca2+ channels, followed by K+ channels
~ 3/min (stomach) to ~ 12/min (duodenum)

More on slow-wave potentials:

Membrane undergoes self-
induced hyperpolarization
and depolarization swings

A burst of action potentials
occurs if a depolarization
swing brings the membrane to threshold

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8
Q

Interstitial cell network in pacemaker region

A

Interstitial Cells of Cajal (ICC) are the pacemakers of the gut
ICCs in region of myenteric plexus (MY-ICCs) are pacemaker cells, and spontaneously generate slow wave depolarizations, and conduct to adjacent smooth muscle cells via low-resistance junctions (gap junctions)
Depolarization of smooth muscle cells leads to activation of l-type calcium channels, Ca2+ entry, and contraction of the smooth muscle cells.
Thus, slow waves naturally organize the contractile pattern of gastric smooth muscles into a series of phasic contractions.

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9
Q

Intramuscular ICC (IM-ICC)

A 
A second class of ICCs lies within circular layers of smooth muscle bundles and are known as intramuscular ICCs (IM-ICCs). 
The IM-ICCs appear to be important in mediating neurotransmission because they form very close, synaptic connections with the varicose terminals of enteric motor neurons (short arrows).
IM-ICCs are also electrically coupled via gap junctions to smooth muscle cells.
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10
Q

action potentials in smooth muscle

A

Generated in response to neural and/or hormonal modulation of membrane
potential to threshold
Typically slower and longer vs. sk. muscle
Depolarization: opening of slow Ca2+ channels (slow inactivation); Na+
Repolarization: delayed opening voltage-gated or Ca2+-activated K+ channels
Minimal “overshoot”

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11
Q

Action potential spikes in smooth muscle: take home message

A

Ca2+ influx, K+ efflux

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12
Q

Phasic contraction vs tonic contraction example locations

A

Phasic- gi tract
tonic- gi Sphincters.

Ca++ stays higher longer in tonic contraction.

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13
Q

useful bits about smooth muscle contractions

A

less fatigue, longer contraction, lower use of ATP - much more efficient than skeletal muscle.

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14
Q

Sources of Ca2+ in Smooth Muscle

A
  1. Voltage-gated Ca2+channels ***
    Extracellular source
    Depolarization (graded, slow-wave, AP: Electromechanical coupling) opens L-type Ca2+channels
  2. Sarcoplasmic reticulum
    a. Ca2+-induced Ca2+ release (CICR) via ryanodine receptor
    b. IP3 Ca2+ channel*
    Pharmacomechanical coupling: hormones & neurotransmitters can initiate increased [Ca2+]i via G-protein coupled receptors (voltage independent***)
  3. Store-operated Ca2+channels (SOCs)
    Extracellular source
    Opening linked to depletion of SR Ca2+ stores
    Voltage independent***
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15
Q

Relaxation in smooth muscle

A

Ca2+ sequestering: SERCA of the SR, Ca2+-ATPase pump (sarcolemma), 3Na+-1Ca2+ antiporter (sarcolemma)

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16
Q

Role of Ca2+ in excitation-contraction coupling of smooth muscle vs skeletal muscle?

A

In sm. Muscle, Ca2+ turns on the X-bridge by inducing a chemical change in Myosin (thick)

 In sk.muscle, Ca2+ invokes a physical change in Actin (thin)
17
Q

activation of myosin

A

4 Ca2+ binds calmodulin
Ca2+- calmodulin complex binds & activates myosin light-chain kinase (MLCK)
Activated MLCK phosphorylates myosin regulatory light chain
Conformational change of myosin head & increased ATPase activity allows actin interaction & power stroke

18
Q

force regulation of smooth muscle contractions

A

Overall: relative balance between phosphorylated and dephosphorylated MLCs
[Ca2+]i
-Affects rate of MLC phosphorylation
Sensitivity to Ca2+ of MLCK
-Affects the degree of contraction at a given [Ca2+]i

19
Q

latch state

A

Maintenance of tension in tonic smooth muscle contractions for prolonged periods of time

  • Relatively low ATP consumption
  • Force maintained at lower level of MLCK phosphorylation
  • Myosin remains attached to actin for longer duration
20
Q

significance of latch state

A

maintenance of smooth muscle tone without fatigue

21
Q

gastric pacesetter myoelectrical activity

A

Peristaltic waves originate in the pacemaker area.
Gastric slow waves linked with plateau potentials (or action potentials), the electrophysiological basis of gastric peristaltic waves.
The plateau and action potentials occur during circular muscle contractions.
The frequency (3 cycles per minute [cpm]) and propagation velocity (approximately 14 mm/second) of the gastric peristaltic waves are controlled by the slow wave, which leads the contraction from the proximal corpus to the distal antrum

22
Q

4 General GI regulatory mechanisms

A

Autonomous Smooth muscle

- Single-unit smooth m. with gap junctions: Electrical Syncytium
- Slow wave potentials: Interstitial cells of Cajal = pacesetters
  1. Extrinsic Nerves
    • Sympathetic and Parasympathetic
    • Coordinate activity in different regions
  2. Intrinsic Nerve Plexuses
    • Submucosal and Myenteric plexuses
    • Local coordination of motility & secretions
  3. Gastrointestinal Hormones
    -Gastrin, Secretin, CCK, GIP
    -Paracrines:
    Somatostatin, Histamine
23
Q

Effects of increased ACh

A

increase salivation, defecation, lacrimation, urination, GIT motility, muscle contraction

24
Q

effects of decreased ACh

A

dry mouth, constipation, urine retention.

25
Q

increased Sympathetic innervation

A

promotes decreased motility and secretions; increased sphincter constriction

26
Q

Intrinsic neural regulation of GI function

A

Enteric Nervous System (ENS)

Division of the autonomic nervous system
Comprised of ~ 100 million neurons
Coordinates and relays parasympathetic and sympathetic inputs to GI tract
Coordinates local reflexes within the GI tract
Controls most GI functions (motility and secretions)
Can act independent of extrinsic innervation

27
Q

Myenteric Plexus

A

= Auerbach’s plexus
-Between the outer longitudinal and inner circular muscle layers of the
muscularis externa throughout the GI tract

primarily controls the motility of the GI smooth muscle

28
Q

Submucosal plexus

A

= Meissner’s plexus
In the submucosa of the large intestins

primarily controls secretion and blood flow

29
Q

sensory receptors

A

mechanoreceptors (distention)
chemoreceptors (pH, nutrients)
osmoreceptors

30
Q

Summary of single-unit smooth muscle characteristics

A

Location- walls of hollow organs in digestive, reproductive, and urinary tracts and in small blood vessels
function- movement of contents within hollow organs
mechanism of contarction- sliding filament mechanism
innervation- autonomics
level of control– involuntary
initiation of contraction- myogenic (pacemaker potentials and slow-wave potentials)
role of nervous stimulation- modifies contraction; can excite or inhibit; contributes to gradation
hormones can modify
thick myosin and thin actin present
not striated
tropomyosin only, no troponin

31
Q

mechanism of Ca2+ action in single-unit smooth muscle

A

chemically brings about phosphorylation of myosin cross bridges so they can bind with actin

32
Q

the 3 major neuromuscular activities of the stomach are

A

(1) receptive relaxation of the fundus;
(2) recurrent peristaltic waves of the corpus and antrum; and
(3) antral peristaltic waves coordinated with antropyloroduodenal coordination.

33
Q

These major neuromuscular activities of the stomach accomplish three key functions

A

(1) to receive the ingested food that we eat (receptive relaxation);
(2) to mill (triturate) ingested foodstuffs into a nutrient suspension termed chyme; and
(3) to empty the chyme from the stomach into the duodenum in a highly regulated
fashion in order to maximize further digestion and absorption of the nutrients.

34
Q

The gastric neuromuscular activities and related functions are modulated by

A

(1) the central nervous system (CNS),
(2) the parasympathetic nervous system (PNS)
(3) sympathetic nervous systems (SNS),
(4) the interactions of the CNS and the activity of the enteric nervous system (ENS),
(5) the interstitial cells of Cajal (ICCs) that regulate the frequency of contractions and
organize peristaltic waves, and
(6) the host of neurotransmitters that ultimately regulate the contraction and
relaxation of gastric smooth muscle.

GI part 2 (16 decks)

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