Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Specialization of the Sarcolemma and Sarcoplasm for Muscular Contraction
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basal lamina also plays an important role in the development
and regeneration of the neuromuscular junction.
The arrival of a nerve action potential at the axon terminal
results in activation of voltage-gated calcium ion
channels in the presynaptic membrane. The calcium influx
initiates a calcium-dependent exocytosis of ACh-containing
vesicles from the active zone of the presynaptic membrane.
Voltage-gated potassium channels in the presynaptic
membrane close the voltage-gated calcium channels and
restore resting membrane potential in the axon. The ACh
released diffuses across the synaptic cleft to bind with acetylcholine
receptors (AChRs), which are concentrated on
the crests of the secondary folds of the postsynaptic sarcolemma.
The structure of the AChR is similar among animal
species. The AChR molecule is an integral transmembrane
protein that is formed of five homologous subunits that
form a central pore through which ions can flow. It consists
of two alpha subunits and single δ , γ , and subunits, which
possesses a binding site for ACh at the external interfaces
of the α / δ and the α / subunits. Somewhat deeper within
the troughs of the secondary folds are voltage-gated
sodium ion channels, which are also present within the sarcolemma
throughout nonjunctional regions of the myofiber
( Engel, 2004 ).
Excitation of the myofiber is initiated by the reversible
binding of ACh with AChRs. The binding of ACh
with AChR (two ACh molecules/receptor) results in a local
depolarization of the postsynaptic membrane caused by the
transient-increased conductance of the AChR cation ion
channels to sodium and potassium ions. The amplitude of
the end-plate potential (depolarization) is proportional to
the number of ACh-AChR complexes formed. At rest, individual
quanta of ACh are spontaneously released at a slow
rate and cause transient, low-amplitude depolarizations at
the end plate. These are referred to as miniature end-plate
potentials (MEEPs). The interior of a resting muscle fiber
has a resting potential of about 95 mV. The binding of
ACh to AChRs is transient, and its effects are abolished by
diffusion of ACh away from the receptors and its hydrolysis
by AChE. With the arrival of a nerve action potential,
approximately 200 quanta of ACh are released, and with
the increased number of ACh-AChR combinations, there
is a greater conductance of sodium and potassium ions
that form a large amplitude depolarization, the end-plate
potential (EEP). When the amplitude of the EEP exceeds
threshold (approximately 50 mV), a wave of depolarization
(muscle action potential, MAP) is generated over the
sarcolemma, away from the end plate in all directions. The
MAP is propagated by voltage-gated sodium channels over
the surface of the myofiber and into its depths via transverse
(T) tubules. The T tubules are invaginations of the
sarcolemma that tranverse the long axis of the myofiber,
and their lumina openly communicate with the extracellular
fluid space ( Engel, 2004 ).
B . Coupling Excitation to Contraction
Excitation-contraction coupling involves the transformation
of depolarizing events in the sarcolemma into the initiation
of mechanical shortening of the myofibrils within the myofiber
by calcium ions released from the terminal cisternae of
the sarcoplasmic reticulum (SR). These events occur within
the depths of the myofiber at “ triads ” where the T tubules
form junctional complexes with adjacent terminal cisternae
of the SR. A triad occurs twice in each sarcomere. The sarcoplasmic
reticulum functions in the uptake, storage, and
release of calcium ions to regulate the concentration of calcium
ions in the aqueous sarcoplasm bathing the myofilaments
and other organelles. The concentration of calcium in
the SR is aided by the presence of calsequestrin, a calciumbinding
protein that is maintained in the lumen of the cisternae
by triadin and junctin.
At the T-SR junctional complex of triads, the sarcolemma
contains voltage-sensitive dihydropyridine receptors
(DHPRs) and the terminal cisternae of the SR possess
ryanodine-sensitive calcium ion channels (ryanodine
receptors) that form “feet ” that fill the gap between the terminal
cisternae and T tubules. Accessory proteins that regulate
ryanodine receptor function include calmodulin and
FK-506 binding protein. With depolarization of the sarcolemma
within the T tubules, DHPRs interact with ryanodine
receptors to mediate the voltage-dependent release of
calcium ions from the SR into the sarcoplasm, elevating
the calcium ion concentration from 10 7 to 10 5 M. This
elevation in calcium ion concentrations initiates contraction
through its interaction with the calcium binding proteins
such as troponin C and calmodulin, a component of
the myosin light chain kinase system ( Magleby, 2004 ).
Relaxation is initiated by a reduction in the sarcoplasmic
calcium ion concentration through active transport of
calcium ions into the lumen of the SR by the SR calcium-
ATPase (SERCA). At low calcium concentrations, SERCA
activity is inhibited by phospholamban. However, relaxation
is promoted by SERCA at higher myoplasmic calcium
concentrations generated by stimulation of the ryanodine
receptor. Further details concerning the structures and functions
involved in neuromuscular transmission and coupling
of excitation to contraction are available elsewhere ( Engel,
2004 ; Magleby, 2004 ; Martonosi and Pikula, 2003 ; Numa
et al. , 1990 ).
C . Muscular Contraction
The ability of skeletal muscle to contract is conferred by
the elementary contractile unit, the sarcomere ( Fig. 15-2 ).
The sarcomere has three crucial properties: (1) the ability to
shorten rapidly and efficiently, (2) the ability to switch on
and off in milliseconds, and (3) precision self-assembly and
structural regularity. There are three major functional classes