Regulation of GI Fuction (muscle) Flashcards
smooth muscle characteristics
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
Smooth muscle innervation
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
2 types of smooth muscle
multiunit smooth
single-unit smooth (visceral smooth, unitary smooth). Gap junctions permit coordinated contraction
multi-unit smooth muscle
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
single-unit (unitary, visceral)
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.
graded potentials in smooth muscle
(not quite action potentials)
Hyperpolarizing or depolarizing
Spatial or temporal summation
Stimuli: mechanical, humoral, neural
slow-wave potentials
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
Interstitial cell network in pacemaker region
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.
Intramuscular ICC (IM-ICC)
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.
action potentials in smooth muscle
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”
Action potential spikes in smooth muscle: take home message
Ca2+ influx, K+ efflux
Phasic contraction vs tonic contraction example locations
Phasic- gi tract
tonic- gi Sphincters.
Ca++ stays higher longer in tonic contraction.
useful bits about smooth muscle contractions
less fatigue, longer contraction, lower use of ATP - much more efficient than skeletal muscle.
Sources of Ca2+ in Smooth Muscle
- Voltage-gated Ca2+channels ***
Extracellular source
Depolarization (graded, slow-wave, AP: Electromechanical coupling) opens L-type Ca2+channels - 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***) - Store-operated Ca2+channels (SOCs)
Extracellular source
Opening linked to depletion of SR Ca2+ stores
Voltage independent***
Relaxation in smooth muscle
Ca2+ sequestering: SERCA of the SR, Ca2+-ATPase pump (sarcolemma), 3Na+-1Ca2+ antiporter (sarcolemma)
Role of Ca2+ in excitation-contraction coupling of smooth muscle vs skeletal muscle?
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)
activation of myosin
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
force regulation of smooth muscle contractions
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
latch state
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
significance of latch state
maintenance of smooth muscle tone without fatigue
gastric pacesetter myoelectrical activity
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
4 General GI regulatory mechanisms
Autonomous Smooth muscle
- Single-unit smooth m. with gap junctions: Electrical Syncytium - Slow wave potentials: Interstitial cells of Cajal = pacesetters
- Extrinsic Nerves
- Sympathetic and Parasympathetic
- Coordinate activity in different regions
- Intrinsic Nerve Plexuses
- Submucosal and Myenteric plexuses
- Local coordination of motility & secretions
- Gastrointestinal Hormones
-Gastrin, Secretin, CCK, GIP
-Paracrines:
Somatostatin, Histamine
Effects of increased ACh
increase salivation, defecation, lacrimation, urination, GIT motility, muscle contraction
effects of decreased ACh
dry mouth, constipation, urine retention.
increased Sympathetic innervation
promotes decreased motility and secretions; increased sphincter constriction
Intrinsic neural regulation of GI function
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
Myenteric Plexus
= 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
Submucosal plexus
= Meissner’s plexus
In the submucosa of the large intestins
primarily controls secretion and blood flow
sensory receptors
mechanoreceptors (distention)
chemoreceptors (pH, nutrients)
osmoreceptors
Summary of single-unit smooth muscle characteristics
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
mechanism of Ca2+ action in single-unit smooth muscle
chemically brings about phosphorylation of myosin cross bridges so they can bind with actin
the 3 major neuromuscular activities of the stomach are
(1) receptive relaxation of the fundus;
(2) recurrent peristaltic waves of the corpus and antrum; and
(3) antral peristaltic waves coordinated with antropyloroduodenal coordination.
These major neuromuscular activities of the stomach accomplish three key functions
(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.
The gastric neuromuscular activities and related functions are modulated by
(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.
