Download Ca 2+

Properties of Muscle
• Contractility
– Ability of a muscle to shorten with force
• Excitability
– Capacity of muscle to respond to a stimulus
• Extensibility
– Muscle can be stretched to its normal resting length and
beyond to a limited degree
• Elasticity
– Ability of muscle to recoil to original resting length
after stretched
Muscle Tissue Types
• Skeletal
– Attached to bones
– Nuclei multiple and peripherally located
– Striated, Voluntary and involuntary (reflexes)
• Smooth
– Walls of hollow organs, blood vessels, eye, glands, skin
– Single nucleus centrally located
– Not striated, involuntary
• Cardiac
– Heart
– Single nucleus centrally located
– Striations, involuntary, intercalated disks
Morphology of Muscle
Four types: skeletal, cardiac, smooth and myoepithelial cells
Long multinucleated cells that
respond only to motor-nerve
signals, which cause Ca release
from sarcoplasmic reticulum and
activation of actin-myosin
interaction.
Shorter mononucleated cells
linked to each other by
intercalated disks that contain
many gap junctions. Capable of
independent, spontaneous
contraction, with electrical
depolarization transmitted from
cell to cell through gap junctions.
Spindle-shaped mononucleated cells. Contraction
influenced by hormones and
autonomic nerves. Contraction
governed through myosin light
chain kinase.
Skeletal muscle
• 40% of adult body weight
• 50% of child’s body weight
• Muscle contains:
– 75% water
– 20% protein
– 5% organic and inorganic compounds
• Functions:
– Movement
– Maintenance of posture
Structure of Thick Filaments
Myosin - 2 heavy chains, 4 light chains
• Heavy chains - 230 kD
• Light chains - 2 pairs of
different 20 kD chains
• The "heads" of heavy chains
have ATPase activity and
hydrolysis here drives
contraction
• Light chains are homologous to
calmodulin
Ca2+
DHPR
RyR
RyR = ryanodine
receptor Ca2+ channel
DHPR = dihydropyridine receptor
Mechanism of muscle contraction
Sliding filament model of muscle contraction
"Crossbridges" form
between myosin and
actin, with myosin pulling
actin into "H zone" and
shortening distance
between Z disks.
Length-tension curve for skeletal muscle
Full overlap between
thick and thin filaments
Decreasing overlap limits
maximum tension
Actin poking
through M line;
myosin bumping
into Z disk.
Contraction range with
normal skeletal movements
No overlap
(Muscles are not naturally
stretched to this point)
Molecular mechanisms of crossbridge action
T-tubules are NOT
positioned at M lines.
Dihydropyridine Receptor
In t-tubules of heart and skeletal muscle
• Nifedipine and other DHP-like molecules bind to the
"DHP receptor" in t-tubules
• In heart, DHP receptor is a voltage-gated Ca2+ channel
• In skeletal muscle, DHP receptor is apparently a
voltage-sensing protein and probably undergoes
voltage-dependent conformational changes
Ryanodine Receptor
The "foot structure" in terminal cisternae of SR
• Foot structure is a Ca2+ channel of unusual design
• Conformation change or Ca2+ -channel activity of DHP receptor apparently
gates the ryanodine receptor, opening and closing Ca2+ channels
2+
Ca
Controls Contraction
• Release of Ca2+ from the SR
triggers contraction
• Reuptake of Ca2+ into SR
relaxes muscle
• So how is calcium released in
response to nerve impulses?
• Answer has come from studies
of antagonist molecules that
block Ca2+ channel activity
This gap is
actually only
~10 nm.
Ca2+-ATPase
Function of Neuromuscular
Junction
acetate + choline
Na+
–
+
–
+
–
+
–
+
–
+
~ +40mV
~ -15mV
+
+
-
-
end-plate
potential (EPP)
~ -15 mV
Summation of skeletal muscle tension; tetanus
Contractile force
can also be
regulated through
activation of
more, or fewer,
motor units.
Muscle contraction
• Types
– Isometric or static
• Constant muscle length
• Increased tension
– Isotonic
• Constant muscle tension
• Constant movement
»
–
Time is required for maximal twitch force to develop, because some
shortening of sarcomeres must occur to stretch elastic elements of
muscle before force can be transmitted through tendons.
By the time this maximal force is developed, [Ca2+] and number of
active crossbridges have greatly decreased, so an individual twitch
reaches much less than the maximum force the muscle can develop.
Generate ATP
* Mitochondria generate ~32 ATP from one glucose
(slow, but efficient).
* Glycolysis generates 2 ATP from one glucose
(fast, but inefficient; lactate accumulates).
* Creatine kinase reaction: (fastest)
ADP + creatine-P  ATP + creatine
Fatigue:
* Central — involving central nervous system
may involve such factors as dehydration, osmolarity,
low blood sugar, and may precede physiological
fatigue of actual muscles.
* Peripheral — in or near muscles
accumulation of lactate and pH, especially in
fast-twitch fibers
 inorganic phosphate — may increasingly inhibit
cleavage of ATP in the crossbridge cycle or in
the sequestering of Ca2+.
– Incomplete tetanus
• Muscle fibers partially
relax between contraction
• There is time for Ca 2+ to
be recycled through the
SR between action
potentials
– Complete tetanus
• No relaxation between
contractions
• Action potentials come sp
close together that Ca 2+
does not get resequestered in the SR
A skeletal muscle twitch lasts far longer than the
refractory period of the stimulating action potential, so
many additional stimuli are possible during the twitch,
leading to summation of tension and even tetanus.
In cardiac muscle, the action potential — and therefore
the refractory period — lasts almost as long as the
complete muscle contraction, so no tetanus, or even
summation, is possible. Sequential contractions are at
the same tension, though gradual increases and
decreases occur with autonomic nervous system input.
Cardiac Muscle
Copyright © 2008
Pearson Education,
Figure 12.37
Treppe
• Graded response
• Occurs in muscle rested
for prolonged period
• Each subsequent
contraction is stronger
than previous until all
equal after few stimuli