MBBS 1st Year Medical Physiology-1(102)-Nerve&Muscle

About 40 per cent of the body is skeletal muscle,
and perhaps another 10 per cent is smooth and
cardiac muscle. Some of the same basic principles of
contraction apply to all these different types of
muscle.

General Mechanism of Muscle
Contraction:
The initiation and execution of muscle contraction
occur in the following sequential steps.
1. An action potential travels along a motor nerve to
its endings on muscle fibers.
2. At each ending, the nerve secretes a small amount
of the neurotransmitter substance acetylcholine.
3. The acetylcholine acts on a local area of the muscle
fiber membrane to open multiple “acetylcholinegated”
channels through protein molecules floatingin the membrane.

4. Opening of the acetylcholine-gated channels allows
large quantities of sodium ions to diffuse to the
interior of the muscle fiber membrane. This initiates
an action potential at the membrane.
5. The action potential travels along the muscle fiber
membrane in the same way that action potentials
travel along nerve fiber membranes.
6. The action potential depolarizes the muscle
membrane, and much of the action potential
electricity flows through the center of the muscle
fiber. Here it causes the sarcoplasmic reticulum to
release large quantities of calcium ions that have
been stored within this reticulum.
7. The calcium ions initiate attractive forces between
the actin and myosin filaments, causing them to
slide alongside each other, which is the contractile
process.
8. After a fraction of a second, the calcium ions are
pumped back into the sarcoplasmic reticulum by a
Ca++ membrane pump, and they remain stored in
the reticulum until a new muscle action potential
comes along; this removal of calcium ions from the
myofibrils causes the muscle contraction to cease.

Contraction of Smooth
Muscle:

We now turn to smooth
muscle, which is composed of far smaller fibers—
usually 1 to 5 micrometers in diameter and only 20
to 500 micrometers in length. In contrast, skeletal
muscle fibers are as much as 30 times greater in diameter and hundreds of times
as long. Many of the same principles of contraction apply to smooth muscle as
to skeletal muscle. Most important, essentially the same attractive forces
between myosin and actin filaments cause contraction in smooth muscle as in
skeletal muscle, but the internal physical arrangement of smooth muscle fibers
is very different.

Types of Smooth Muscle:
The smooth muscle of each organ is distinctive from that of most other organs
in several ways: (1) physical dimensions, (2) organization into bundles or sheets,
(3) response to different types of stimuli, (4) characteristics of innervation, and
(5) function. Yet, for the sake of simplicity, smooth muscle can generally be
divided into two major types: multi-unit smooth
muscle and unitary (or single-unit) smooth muscle.

Regulation of Smooth Muscle Contraction:
As is true for skeletal muscle, the initiating stimulus
for most smooth muscle contraction is an increase in
intracellular calcium ions. This increase can be caused
in different types of smooth muscle by nerve stimulation
of the smooth muscle fiber, hormonal stimulation,
stretch of the fiber, or even change in the chemical
environment of the fiber.
Yet smooth muscle does not contain troponin, the
regulatory protein that is activated by calcium ions
to cause skeletal muscle contraction. Instead, smooth
muscle contraction is activated by an entirely different
mechanism, as follows.
Combination of Calcium Ions with Calmodulin—Activation of
Myosin Kinase and Phosphorylation of the Myosin Head. In
place of troponin, smooth muscle cells contain a large
amount of another regulatory protein called calmodulin.
Although this protein is similar to troponin, it is
different in the manner in which it initiates contraction.
Calmodulin does this by activating the myosin
cross-bridges. This activation and subsequent contraction
occur in the following sequence:
1. The calcium ions bind with calmodulin.
2. The calmodulin-calcium combination joins with
and activates myosin kinase, a phosphorylating
enzyme.
3. One of the light chains of each myosin
head, called the regulatory chain, becomes
phosphorylated in response to this myosin kinase.
When this chain is not phosphorylated, the
attachment-detachment cycling of the myosin
head with the actin filament does not occur. Butwhen the regulatory chain is phosphorylated, the
head has the capability of binding repetitively
with the actin filament and proceeding through
the entire cycling process of intermittent “pulls,”
the same as occurs for skeletal muscle, thus
causing muscle contraction.

Special Characteristics
of Signal Transmission
in Nerve Trunks:
Myelinated and Unmyelinated Nerve Fibers-
many large nerve fibers that constitute most of the
cross-sectional area. However, a more careful look
reveals many more very small fibers lying between
the large ones. The large fibers are myelinated, and the
small ones are unmyelinated. The average nerve trunk
contains about twice as many unmyelinated fibers as
myelinated fibers. The
central core of the fiber is the axon, and the membrane
of the axon is the membrane that actually conducts the
action potential.The axon is filled in its center with axoplasm,
which is a viscid intracellular fluid. Surrounding
the axon is a myelin sheath that is often much thicker
than the axon itself. About once every 1 to 3 millimeters
along the length of the myelin sheath is a node of Ranvier.

Physiologic Anatomy of the Neuromuscular Junction—The Motor End Plate- The nerve fiber forms a complex of branching nerve
terminals that invaginate into the surface of the muscle fiber but lie outside the
muscle fiber plasma membrane. The entire structure is called the motor end
plate. It is covered by one or more Schwann cells that insulate it from the
surrounding fluids. The invaginated membrane
is called the synaptic gutter or synaptic trough, and the space between the
terminal and the fiber membrane is called the synaptic space or synaptic cleft.
This space is 20 to 30 nanometers wide. At the bottom of the gutter are numerous
smaller folds of the muscle membrane called subneural clefts, which greatly
increase the surface area at which the synaptic transmitter can act.
In the axon terminal are many mitochondria that supply adenosine triphosphate
(ATP), the energy source that is used for synthesis of an excitatory
transmitter acetylcholine. The acetylcholine in turn excites the muscle
fiber membrane. Acetylcholine is synthesized in the cytoplasm of the terminal,
but it is absorbed rapidly into many small synaptic vesicles, about 300,000
of which are normally in the terminals of a single end plate. In the synaptic
space are large quantities of the enzyme acetylcholinesterase, which destroys
acetylcholine a few milliseconds after it has been released from the synaptic
vesicles.

The Lipid Barrier of the Cell Membrane,
and Cell Membrane Transport Proteins:
This membrane
consists almost entirely of a lipid bilayer, but it also contains large numbers of
protein molecules in the lipid, many of which penetrate all the way through the
membrane.
The lipid bilayer is not miscible with either the extracellular fluid or the intracellular
fluid. Therefore, it constitutes a barrier against movement of water
molecules and water-soluble substances between the extracellular and intracellular
fluid compartments. However, as demonstrated in Figure 4–2 by the leftmost
arrow, a few substances can penetrate this lipid bilayer, diffusing directly
through the lipid substance itself; this is true mainly of lipid-soluble substances,
as described later.
The protein molecules in the membrane have entirely different properties for
transporting substances. Their molecular structures interrupt the continuity of
the lipid bilayer, constituting an alternative pathway through the cell membrane.
Most of these penetrating proteins, therefore, can function as transport
proteins. Different proteins function differently. Some have watery spaces all
the way through the molecule and allow free movement of water as well as
selected ions or molecules; these are called channel proteins. Others, called
carrier proteins, bind with molecules or ions that are to be transported; conformational
changes in the protein molecules then move the substances through
the interstices of the protein to the other side of the membrane. Both the
channel proteins and the carrier proteins are usually highly selective in the types
of molecules or ions that are allowed to cross the membrane.