Muscles general information

Vertebrates and many invertebrates have three main classes of muscle

Skeletal muscle
Smooth muscles surround internal organs such as the large and small
intestines, the uterus, and large blood vessels
Cardiac muscle: Striated muscle of the heart.
Smooth Muscle - introduction
Slow, regular contractions
Prolonged contractions
Contribute to many systems
Key differences from skeletal muscle
Lack sarcomeres (no striations)
No t-tubules
Minimal SR
Gap junctions
Contract in all dimensions
More complex regulation
Smooth muscles - introduction
Smooth muscle cells have multiple receptors and activation mechanisms
Smooth muscle cells can be activated by neurotransmitters, hormones,
neighbouring cells
Example: Electrical coupling through gap junctions synchronizes the
contractions of the smooth muscle cells responsible for the peristaltic
movements of the intestine
Important: The overall goal is always the same.... change levels of
cytosolic Ca
2+
to change the degree of contraction.
Another example: In a blood vessel there are spontaneously active
pacemaker cells which can be conducted across a few or many cells.
Some smooth muscle cells have fast contractions while other are slower
or maintain muscle tone or sustained contractions for long periods of
time
Smooth muscles more introduction
The sarcoplasmic reticulum network is sparse
Majority of the increase in cytosolic Ca
2+
needed for muscle contraction
enters the cell via the plasma-membrane Ca
2+
channel
This means that changes in the cytosolic Ca
2+
level occur much more
slowly in smooth muscle (seconds to minutes).
This has the advantage of allowing the slow, steady response in
contractile tension that is required by vertebrate smooth muscle.
Contraction in some smooth muscle cells are controlled by changes in
membrane potential and some are purely through chemical/hormone
processes
Nerve innervation of smooth muscle cells is from the autonomic nervous
system and similar to cardiac muscle cells works over a wide area of
general neurotransmitter release
The function of neurotransmitters is usually to modulate contraction
rather than initiate contraction
Many smooth muscle cells have the ability to spontaneously activate
Contractions can occur over minutes rather than milliseconds as was
seen with skeletal and hundreds of milliseconds as was seen with
cardiac cells.
Smooth muscles more introduction
A smooth muscle is composed of elongated spindle-shaped cells, each
with a single nucleus
Packed with thick and thin filaments but these filaments are not
organized into well-ordered sarcomeres and thus smooth muscle is not
striated
Filaments in smooth muscle are gathered into loose bundles, which are
attached to dense bodies in the cytosol
Dense bodies apparently serve the same function as Z disks in skeletal
muscle
The other end of the thin filaments in many smooth muscle cells is
connected to attachment plaques, which are similar to dense bodies but
are located at the plasma membrane of a muscle cell
Like a Z disk, an attachment plaque is rich in the actin-binding protein
alpha-actinin; it also contains a second protein, vinculin, which binds to
an integral membrane protein in the plaque and to alpha-actinin, thereby
attaching actin filaments to membrane adhesion sites.
Smooth muscles
Smooth muscle contraction
Smooth muscle contraction is not controlled by the binding of Ca
2+
to
the troponin complex as it is in cardiac and skeletal muscles
Ca
2+
control of myosin attachment to the actin is through an
intermediate step of Ca
2+
/calmodulin and it is this that controls
contraction in smooth muscle cells
Calmodulin = intracellular second messenger that binds Ca
2+

Troponin is not found in smooth muscle cells (tropomyosin is)
Caldesmon = regulatory protein on smooth muscle actin. Binds to actin
and prevents myosin from binding actin
Caldesmon and Ca
2+
/calmodulin
The activation of smooth muscle myosin can be regulated by caldesmon
(CD) which in low Ca
2+
levels (10
-6
M), binds to tropomyosin and actin and
blocks myosin binding to actin
As Ca
2+
levels increase, Ca
2+
activated calmodulin binds to caldesmon
which releases caldesmon from the tropomyosin/actin complex
Now myosin is free to bind and move along the thin filaments to contract
the cell
Phosphorylation by several kinases, including MAP kinase, and
dephosphorylation by phosphatases also regulate caldesmons actin-
binding activity
*
*
*
Myosin light chain kinase (MLCK) and Ca
2+
/calmodulin
In vertebrate smooth muscle, phosphorylation of the myosin regulatory
light chains on site X by Ca
2+
-dependent myosin LC kinase activates
contraction
At Ca
2+
concentrations <10
-6
M, the myosin LC kinase is inactive
A myosin LC phosphatase, which is not dependent on Ca
2+
for activity,
dephosphorylates the myosin LC, causing muscle relaxation
Myosin light chain kinase and Ca
2+
/calmodulin
Two enzymes control this process:
Myosin light chain kinase (MLCK) and myosin light chain phosphotase
One of the two myosin light chain pairs associated with the myosin in
smooth muscle inhibits actin stimulation of the myosin ATPase activity at
low Ca
2+
concentrations
Phosphorylation of the myosin light chain by MLCK removes this
inhibition and the smooth muscle contracts
MLCK is activated by Ca
2+
through calmodulin
Ca
2+
binds to calmodulin, and the Ca
2+
-calmodulin complex then binds to
MLCK and activates it
Because this mode of regulation relies on the diffusion of Ca
2+
and the
action of protein kinases, muscle
contraction is much slower in smooth
muscle than in skeletal muscle.
The greater the amount of intracellular Ca
2+

the more MLCK is activated and the greater
the degree of contraction

Contraction simple
Intracellular Ca
2+
increase and Ca
2+
is
released from the SR
Ca
2+
binds to calmodulin (CaM)
Ca
2+
- calmodulin complex activates
MLCK
MLCK phosphorylates light chains in
myosin heads and increases myosin
ATPase activity
Active myosin crossbridges slide along
actin and create muscle
*
*
*
*
*
*
Relaxation - simple
Free Ca
2+
in cytosol decreases when
Ca
2+
is pumped out of the cell or back
into the SR released from the SR
Ca
2+
unbinds from calmodulin
Myosin phosphatase removes
phosphate from myosin, which
decreases myosin ATPase
Less myosin ATPase activity results in
decreased muscle tension
*
*
*
*
Regulation of smooth muscle contraction
The major means that control smooth muscle contraction is controlled
is through changes in resting membrane potential
Depolarization causes a greater increase in cytosolic Ca
2+
and thus
greater contraction
Hyperpolarization causes a reduced amount of cytosolic Ca
2+
and thus
relaxes the muscle cell
However it is important to note that release of Ca
2+
from internal stores
may also lead to greater contraction through G protein mediated
cascades that have nothing to do with changes in membrane
depolarization.
Norepinephrine and epinephrine
Depending on the type of receptor norepinephrine and epinephrine can
have different results on the smooth muscle cell
Epinephrine bound to beta-adrenergic receptors on smooth muscle cells
of the intestine causes them to relax
Epinephrine also binds to the alpha2-adrenergic receptor found on
smooth muscle cells lining the blood vessels in the intestinal tract, skin,
and kidneys
Epinephrine bound to alpha2 receptors causes the arteries to contract
(constrict), reducing circulation to these organs
Acetylcholine and Nitric Oxide
ACH is released by autonomic nerves in the walls of a blood vessel, and
it causes smooth muscle cells in the vessel wall to relax
ACH acts indirectly by inducing the nearby endothelial cells to make and
release NO, which then signals the underlying smooth muscle cells to
relax.
Regulation of contractility of arterial smooth muscle by NO and cGMP:
NO synthesized in endothelial cells diffuses locally through tissue
and activates guanylate cyclase in nearby smooth muscle cells
The resulting rise in cGMP leads to the relaxation of the muscle and
vasodilation.
Cont..
Acetylcholine and Nitric Oxide
Schematic diagram of the structure of soluble guanylate cyclase
Binding of NO to the heme group stimulates the enzymes catalytic
activity, leading to formation of cGMP from GTP.

More about Nitric Oxide
NO gas is catalyzed by the enzyme NO synthase from arginine
It passes readily across membranes and rapidly diffuses out of the cell
into neighboring cells
NO has a very short half life (5-10 seconds) - so acts only locally
In many target cells, NO binds to iron in the active site of the enzyme
guanylyl cyclase, stimulating this enzyme to produce cyclic GMP.
The effects of NO can occur within seconds, because the normal rate of
turnover of cyclic GMP is high
Increased cGMP activates a kinase that subsequently leads to the
inhibition of calcium influx into the smooth muscle cell, and decreased
calcium-calmodulin stimulation of myosin light chain kinase (MLCK).
This in turn decreases the phosphorylation of myosin light chains,
thereby decreasing smooth muscle tension development and causing
vasodilation.

Other evidence suggests that cGMP works through a kinase (cGMP
dependent protein kinase PKG) that in turn phosphorylates a K
+
channel
to activate and thus hyperpolarize the muscle cell
Other regulators
Nitroglycerine
Has been used for about 100 years to treat patients with angina (pain
resulting from inadequate blood flow to the heart muscle)
Nitroglycerine is converted to NO, which relaxes blood vessels
This reduces the workload on the heart and reduces the oxygen levels
needed by the heart muscle.


Viagra
The drug sildenafil [Viagra] inhibits this cyclic GMP phosphodiesterase
and increases the amount of time that cyclic GMP levels remain elevated.
The cyclic GMP keeps blood vessels relaxed and in certain parts of the
male anatomy blood pools and the resulting effect has sales of Viagra
soaring. It is interesting to note however that Viagra is not specific to the
penis it will affect cGMP levels throughout the body and can have some
interesting side effects.
More about ACH
Tissue Effects of ACh

Vasculature (endothelial cells)
Release of endothelium-derived
relaxing factor (nitric oxide) and
vasodilation
Eye iris (pupillae sphincter muscle) Contraction and miosis
Ciliary muscle
Contraction and accommodation of lens
to near vision
Salivary glands and lacrimal glands Secretionthin and watery
Bronchi Constriction, increased secretions
Heart
Bradycardia, decreased conduction
(atrioventricular block at high doses),
small negative inotropic action
Gastrointestinal tract
Increased tone, increased
gastrointestinal secretions, relaxation at
sphincters
Urinary bladder
Contraction of detrusor muscle,
relaxation of the sphincter
Sweat glands Diaphoresis
Reproductive tract, male Erection
Uterus
Variable, dependent on hormone
influence
Smooth muscles
End of smooth muscle

Cardiac muscle general info
Many similar properties to skeletal muscles but there are some
important differences
Hearts of course vary greatly in size, shape and complexity from
animal to animal - ranging from insects with a simple tube that
pumps blood or hemolymph around an open circulatory system to
our closed circulatory system and a four chambered heart
Cardiac muscle
Cardiac muscle general info
1) The heart contains pace-maker cells that produce the depolarization and
action potentials to drive cardiac cell contraction
Heart contraction is not neuronally driven but self-driven or myogenically.
Some vertebrates hearts are innervated by neurons from the sympathetic
and parasympathetic nervous systems but these neurons act in a
modulatory function only

2) Each muscle cell is a single cell not multinucleate like skeletal muscle
Like skeletal muscle cells each cell contains multiple myofibrils and in the
cases of higher vertebrates an extensive sarcoplasmic reticulum
Depending on the size of the cardiac muscle cells contraction can depend
on Ca
2+
release from the SR and/or Ca
2+
influx from external sources
outside the cell

3) Cardiac muscle cells are linked to each other with gap junctions
Allows an action potentials to rapidly travel from cell to cell and makes the
heart work as a unit.
Allows the pacemaker cells, the sinoatrial node cells, to generate the
action potential which is in turn relayed via the gap junctions throughout
the heart to generate contraction through out the heart.

Cardiac muscle general info cont.
4) There are different types of cardiac muscle cells ranging from the
pacemaker cells in the sinoatrial node to the atrial and ventricular
cells that produce the contraction of the heart chambers

5) The action potential in cardiac cells is quite different from skeletal
muscle and neuronal action potentials in that voltage-gated Ca
2+

channels play a much larger role

6) The mechanism of triggering the Ca
2+
release channel in the
sarcoplasmic reticulum is not the same as in vertebrate skeletal
muscle cells
Pacemaker Cells
Derived from cardiac muscle cells
Differences from most cardiac muscle
Small with few myofibrils, mitochondria or other organelles
Do not contract
Have unstable resting membrane potential (pacemaker potential)
that slowly drifts upwards until it reaches a threshold and
activates and action potential
Cardiac muscle channels and action potentials
Pumps and transporters
1) Na
+
/K
+
ATPase pump - to establish the electrochemical gradients of
Na
+
and K
+
2) Ca
2+
ATPase pump - uses energy from ATP to remove 2 Ca
2+
from
the inside to the outside of the cell or into the sarcoplasmic reticulum
to ensure that internal Ca
2+
concentrations remain low (10
-7
mM
internal)
Some cardiac cells (i.e. lower vertebrates, invertebrates) do not have
an extensive sarcoplasmic reticulum and thus most of the Ca
2+
that is
used to trigger contraction is from extracellular sources
3) Na
+
/Ca
2+
cotransporter - to also remove Ca
2+
from the inside of the
cell and uses the energy from the cotransport of 3 Na
+
molecules to
export 1 Ca
2+
.

Excitation-contraction coupling
Cardiac muscle channels and action potentials
Channels
1) leak channels - leak K
+
channel
2) voltage-gated Na
+
channels
There is a skeletal muscle voltage-gated Na
+
channel which properties
very much like the neuronal voltage-gated Na
+
channel
Responsible for the production of the action potential
3) voltage-gated K
+
channel - the delayed rectifier K
+
channel
4) voltage gated Ca
2+
channels
In cardiac cells the Ca
2+
channel plays a much greater role during the
action potential
These channels are the high threshold Ca
2+
channels, called L
channel or DHP (dihydropyridine channel)
The cardiac DHP channel is very similar to the skeletal muscle DHP
Ca
2+
channel and are found concentrated in the T-tubules in those
cardiac cells with extensive T-tubules and SR.

Action potential in ventricular (and atrial) cardiac cells
4) Resting potentials in these cells is set by a large K
+
permeability due
to a combination of the leak K
+
channel and a voltage-gated K
+
channel
(called the inward rectifier K+ channel) that is open at rest
This means that rest is very close to EK
+

0) The rising phase of the action potential is set by the cardiac voltage-
gated Na
+
channel
Action potential in ventricular (and atrial) cardiac cells
1-2) As the voltage-gated Na
+
channels produce the rising phase and
then start to inactivate two channels will now be opening, the delayed
rectifier K
+
channel and the voltage-gated Ca
2+
channel (L or DHP
channel)
There are many Ca
2+
channels in these cells and thus this channel
dominates the membrane potential producing a long plateau of
depolarization
This plateau is a balance between the open Ca
2+
channels and the open
K
+
channels
Ca
2+
channel only slowly inactivates and thus this plateau can persist for
100-200 msec.

Action potential in ventricular (and atrial) cardiac cells
3) Finally the voltage-gated Ca
2+
channel inactivates and the voltage-
gated K
+
channels will now dominate and the membrane potential will
repolarize to rest (EK
+
in these cells).
Then the voltage-gated K
+
channels will close, the voltage-gated Na
+

channels will switch from the inactive to the closed state and the
membrane is set back at 4) ready to fire again.
The long Ca
2+
plateau allows Ca
2+
inside the cell to elevate enough to
generate contraction in the case of those cardiac cells that rely on
external Ca
2+
sources.
Action potential in sinoatrial cardiac cells
Sinoatrical cells have the ability to spontaneously fire action potentials
in a repeated fashion without any external influence.
These cells are the pacemaker cells of the heart and once an action
potential fires in these cells it is propagated via gap junctions to other
regions of the heart first to the atrial cells and then eventually making it
to the ventricular cells.
Action potential in sinoatrial cardiac cells
The generation of the action potential in these cells is very similar to the
ventricular cardiac cells with a few major exceptions
1) These cells do not have a stable rest. There is a spontaneous slow
depolarization that brings the membrane from -60 mV to threshold for
the action potential (about -40 mV)
2) The action potential is driven by the voltage-gated Ca
2+
channel in
most SA cells
3) The rising phase is due the opening of the voltage-gated Ca
2+
channel
(L or DHP channel again) and thus is slower than in other excitable cells
As the Ca
2+
channel inactivates the membrane is repolarized by the
delayed rectifier K
+
channel as in other excitable cells
4) What makes these cells then spontaneously depolarize once the
delayed K
+
channel has closed is the presence of an ion channel that is
activated by hyperpolarization.
A channel that opens when the membrane becomes repolarized and
allows Na
+
to flow into the cell
Called the funny channel in some literature
Na
+
influx will depolarize the membrane to open the voltage-gated Ca
2+

channels and at the same time close the funny channel.
The funny channel
This unusual cation channel is activated by hyperpolarization
As the membrane repolarizes after the action potential the threshold for
opening of the funny channel is reached at about -50 mV
The channel opens and allows Na
+
to preferentially flow into the cell
The funny channel is also called the HCN channel or hyperpolarization,
cyclic nucleotide gated ion channel
cAMP can have dramatic influences on this channel and shift its
threshold of activation from -50 mV to -40 mV.
The funny channel actually looks very much like a voltage-gated K
+

channel but has differences in its pore to allow Na
+
influx and in the
voltage sensing/opening mechanism.
Putting it all together
Located in the right atrium at the superior vena cava is the sinus node
(sinoatrial or SA node) which consists of specialized muscle cells
The SA nodal cells are self-excitatory, pacemaker cells
They generate an action potential at the rate of about 70 per minute in
humans (your heart beat)
From the sinus node, activation propagates throughout the atria, but
cannot propagate directly across the boundary between atria and
ventricles
This boundary serves to ensure a delay between the activation of the
atria and the ventricles
The atrioventricular node (AV node) is located at the boundary between
the atria and ventricles
In a normal heart, the AV node provides the only
conducting path from the atria to the ventricles
Putting it all together
Propagation from the AV node to the ventricles is provided by a
specialized muscle cells called the bundle of His conduct the signal
system
Further down the bundle separates into two bundle branches which
travel along each side of the septum, constituting the right and left
bundle branches.
Even more distally the bundles split into Purkinje fibers that branch and
contact the inner sides of the ventricular walls.
From the inner side of the ventricular wall, these activation sites cause
the formation of a wave of depolarization which propagates through gap
junctions between the ventricular cells toward the outer wall
After each ventricular muscle region has
depolarized, repolarization occurs.
Electrocardiogram - ECG
The different potential generated in the heart can be measured using an
electrocardiogram.
An ECG is a recording of the electric potentials being generated during
heart activity
The potentials ("waves") are registered by electrodes placed on certain
parts of the body and measure changes in potential (mV)
P wave - an impulse is generated at the sinoatrial node and spreads
across both atria, causing them to contract
Delay: The Fibro-fatty atrioventricular groove insulates the ventricles
from the atrial impulse
The AV node is the only normal gateway of conduction to the ventricles
QRS wave - The impulse travels down the AV bundle and it's branches
and reaches the Purkinje fibers
The ventricles are stimulated to contract
T wave - correlates with repolarization of the
ventricles.
Electrocardiogram - ECG
Electrocardiogram - ECG
Increasing the heart rate
Epinephrine and norepinephrine
Released from the sympathetic nervous system
Epinephrine and norepinephrine are synthesized and released into the
blood by the adrenal medulla, an endocrine organ
Epinephrine and the related norepinephrine are all synthesized from
tyrosine and contain the catechol moiety; hence they are referred to as
catecholamines
Nerves that synthesize and use epinephrine or norepinephrine are
termed adrenergic
Adrenergic receptors: bind epinephrine and norepinephrine. Because
different receptors are linked to different G proteins, the activation leads
to different signal transduction cascades
More Na
+
and Ca
2+
channels open
Rate of depolarization and action potentials increase

Increasing the heart rate cont.
Epinephrine and norepinephrine cont.
In sinoatrial cells: norepinephrine binds to the b-adrenergic receptor
which is a G protein associated membrane receptor
This triggers a signal transduction cascade outlined below that activates
the G protein (Gs - stimulates) that activates adenylate cyclase to
produce cAMP.
Beta-blockers: Drugs which are used to slow heart contractions in the
treatment of cardiac arrhythmia and angina, are beta1-adrenergic
receptor antagonists
They bind the beta1-adrenergic receptor to block the receptor and thus
slow heart contraction
Cardiac muscle cells possess beta1 adenergic receptors
Decreasing the heart rate
Acetylcholine: released from parasympathetic nervous system
Muscarinic acetylcholine receptor: a G protein associated receptor.
The G protein activated in this case is a Gi subunit that inhibits
adenylate cyclase
More K
+
channels open
Pacemaker cells hyperpolarize
Time for depolarization takes longer
Modulating the funny channel
Through G protein coupled receptors various
hormones/neurotransmitters or drugs can increase or decrease the heart
rate by simply increasing or decreasing the ability of the funny channel
to open.
Modulating the funny channel
Activation of adenylyl cyclase following binding of an appropriate
hormone (e.g., epinephrine, glucagon) to a Gs protein coupled receptor
Following ligand binding to the receptor, the Gs protein relays the
hormone signal to the effector protein, in this case adenylyl cyclase
Gs cycles between an inactive form with bound GDP and an active form
with bound GTP
Dissociation of the active form yields the Gsalpha GTP complex, which
directly activates adenylyl cyclase
Activation is short-lived because GTP is rapidly hydrolyzed
The increase in cAMP physically binds to the funny channel and makes
the channel open more easily
In other words the threshold for opening shifts from around -50 mV to
around -40 mV
Therefore the funny channel will open sooner during the repolarization
stage of the sinoatrial action potential and a second action potential will
be triggered sooner
This means that a second wave of action potential and thus contraction
will travel through the heart sooner ie. a faster heart rate.
Modulating the funny channel
Modulation of Ca
2+
channel
Epinephrine also causes an increase in cAMP that stimulates PKA
(protein kinase A) which in turn phosphorylates the voltage-gated Ca
2+

channel (L channel)
This phosphorylation results in a protein conformational change that
enhances the channels activity
This new conformation of Ca
2+
channel opens more readily (i.e. less time
between action potentials) and opens for longer (i.e. more Ca
2+
flow into
the cell = greater [Ca
2+
] intracellular = greater contraction).
Epinephrine also stimulates glycogen breakdown in skeletal muscles
During periods of concentrated activity the glycogen energy stores of
muscles can be mobilized
Caffeine (mmmmhhh): blocks the activty of phosphodiesterases.
Phosphodiesterases break down cyclic nucleotides
Therefore in the presence of caffeine cAMP levels remain elevated and
thus the funny channel continues to open more readily
Therefore the sinoatrial action potential fires more frequently and heart
rate is increased.
Also affects the Ca
2+
release channel or ryanodine receptor such that
more Ca
2+
is released through the channel. Therefore heart contractions
are stronger in the presence of caffeine as well
Modulating the funny channel
Acetylcholine works to block any rise in cAMP and reduces cAMP
levels in the cell
Therefore the funny channel will now not open so readily and the slow
depolarziation of the membrane will occur later thus resulting in a
longer time to generate a second action potential.
Modulating the voltage-gated K
+
channels
Acetylcholine-induced opening of K
+
channels in the heart muscle
plasma membrane
Binding of ACH by muscarinic ACH receptors triggers activation of a
transducing G protein by catalyzing exchange of GTP for GDP on the
alpha subunit
The released beta/gamma subunit then binds to and opens a K
+
channel
The increase in K
+
permeability hyperpolarizes the membrane, which
reduces the frequency of heart muscle contraction
Activation is terminated when the GTP bound alpha subunit is
hydrolyzed to GDP and Galpha GDP recombines with Gbeta/gamma.
Modulating the voltage-gated K
+
channels
Application of acetylcholine (or muscarine) to frog heart muscle produces,
after a lag period of about 40 ms (not visible in graph), a hyperpolarization
of 2 3 mV, which lasts several seconds
From receptor to control of muscle cell contraction
From receptor to control of muscle cell contraction
The cardiovascular system is highly regulated so that there is always an
adequate supply of oxygenated blood to the body tissues under a wide
range of circumstances
There are receptors that respond to the degree of blood pressure and
provide mechanical (barosensory) information about pressure in the
arteries system
There are receptors that provide information about the level of oxygen
and carbon dioxide in the blood
These sensory systems provide input to the respiratory control centers
of the brain which in turn control the parasympathetic and sympathetic
nerves that will control the heart, blood vessels and diaphragm muscles
for breathing.
From receptor to control of muscle cell contraction
We will concentrate only on the chemoreceptors which are located
primarily in the carotid bodies
These are small, specialized organs located at the bifurcation of the
common carotid arteries (some chemosensory tissue is also found in the
aorta)
The chemoreceptors in the carotid bodies and aorta provide information
about the partial pressure of oxygen (pO2) and carbon dioxide (pCO2) in
the blood
This information is relayed by second order neurons to the hypothalamus
and other regions in the brainstem
This information about blood gas levels works in a reflex to modulate the
autonomic nervous system to control smooth and cardiac muscles
It is a balance between regulation of the sympathetic versus
parasympathetic system to up or down regulate cardiac or smooth
muscle contraction.
From receptor to control of muscle cell contraction
The carotid chemosensory cells detect levels of pO2 in the blood by
simply depolarizing in response to decreased levels of oxygen
The mechanism appears to be an O2 sensitive K
+
channel, that in the
presence of normal levels of pO2 is open
Therefore the Vm is close to EK
+

As oxygen levels drop the K
+
channel closes and Vm depolarizes
allowing the voltage-gated Ca
2+
channel to open and to trigger vesicle
fusion and neurotransmitter release
From receptor to control of muscle cell contraction
PO
2
levels can have a direct effect on smooth muscles around blood
vessels
Many of these cells have K
+
channel that is inhibited by ATP
As PO
2
drops so does respiration and ATP production
This reduction in ATP results in the opening of K
+
channels and the
inhibition of smooth muscle contraction
This results in the relaxation of the smooth muscles the relaxation of the
blood vessels and the increase blood flow into the tissue that is
experiencing reduced PO
2

Conversely an increase in PO
2
results in greater inhibition of the ATP
sensitive K
+
channels and thus a greater degree of depolarization
More Ca
2+
channels are open and thus there is greater cytosolic Ca
2+

levels, greater degree of smooth muscle contraction
This causes the blood vessel to constrict (vasoconstriction) and less PO
2

transfer to the surrounding tissues.
From receptor to control of muscle cell contraction