BT_PO 1.98b - Smooth muscle Phys Flashcards
(8 cards)
Discuss and compare the different types of smooth muscle units
Single unit (syncytial, visceral or unitary)
a mass of hundreds to thousands of fibers that contract together as a single unit
fibers arranged in sheets or bundles
cell membranes are adherent to one another at multiple points so that force generated in one muscle fiber can be transmitted to the next.
gap junctions in cell membranes through which ions, APs or inion flow without APs can flow freely from one muscle cell to the next so that action potentials, or ion flow can travel between fibers –> fibers to contract together.
major share of control is exerted by non- nervous stimuli.
found in the walls of most viscera of the body, including the gastrointestinal tract, bile ducts, ureters, uterus, and many blood vessels.
Multi-unit
discrete, separate, smooth muscle fibers
Each fiber operates independently of the others and often is innervated by a single nerve ending, as occurs for skeletal muscle fibers.
Outer surface covered by a thin layer of basement membrane–like substance, a mixture of fine collagen and glycoprotein that helps insulate the separate fibers from one another.
each fiber can contract independently of the others
their control is exerted mainly by nerve signals
the ciliary muscle of the eye, iris muscle and piloerector muscles
Describe the innervation of smooth muscle
In general, smooth muscle is innervated by the autonomic nervous system.
Acetylcholine released by parasympathetic nerves causes contraction (excitation) mediated by muscarinic receptors on the smooth muscle cell in some organs but may be an inhibitory mediator in others.
When acetylcholine excites a smooth muscle cell, norepinephrine inhibits it.
The smooth muscles of the uterus are not innervated.
Some smooth resemble skeletal muscle as they are primarily controlled by motor nerves from the central nervous system.
E.g. arteriolar vasoconstrictor smooth muscles and adrenergic nerves
Other smooth muscles, including those of the viscera, are autorhythmic and contraction is only modified by nerve activity.
Salient anatomical features of smooth muscle
not striated.
Actin filaments
form the contractile units are attached to dense bodies, which are dispersed inside the cell and held together by a scaffold of structural proteins.
The ends of these filaments overlap with a myosin filament located midway between the dense bodies.
5 - 10 x as many actin filaments as myosin filaments are usually found.
Some of the membrane- dense bodies of adjacent cells are bonded together by intercellular protein bridges. It is mainly through these bonds that the force of contraction is transmitted from one cell to the next.
Myosin filaments
interspersed among the actin filaments,
diameter > 2x that of actin filaments
most of the myosin filaments have “side polar” cross- bridges arranged so that the bridges on one side hinge in one direction, and those on the other side hinge in the opposite direction. This configuration allows the myosin to pull an actin filament in one direction on one side while simultaneously pulling another actin filament in the opposite direction on the other side. The value of this organization is that it allows smooth muscle cells to contract as much as 80% of their length instead of being limited to less than 30%, as occurs in skeletal muscle.
have one nucleus
are ~ 1-5µm in diameter and up to 20-500 µm long
held in bundles by connective tissue.
Troponin is absent and its regulatory role is taken over by calmodulin.
Poorly developed sarcoplasmic reticulum (SR); most Ca2+ derived from ECF
Caveolae instead of transverse tubules
When AP is transmitted into caveolae, is believed to excite Ca2+ ion release from abutting SR
Salient features of smooth muscle physiology (cf. Skeletal muscle)
RMP ~ −50 to −60 mV.
most smooth muscle contractions are prolonged and tonic in nature, (may be hrs to days).
Cycling of cross-bridges
rate of myosin cross-bridge attachment and release with actin (‘cross-bridge’ cycling) is much slower in smooth than in skeletal muscle (1/10 to 1/300x less)
The fraction of time that the cross-bridges remain attached to the actin filaments, is greatly ↑ in smooth muscle
Theory: the cross-bridge heads have far less ATPase activity than in skeletal muscle; thus, degradation of the ATP that energizes the movements of the cross- bridge heads is ↓↓, with corresponding ↓ the rate of cycling.
Energy requirements
1/10 to 1/300 x required to sustain the same tension of contraction
1 molecule of ATP is required for each cycle, regardless of its duration.
important to the overall energy economy of the body because organs such as the intestines, urinary bladder, gallbladder, and other viscera often maintain tonic muscle contraction almost indefinitely.
Timing/duration of contraction
begins to contract 50 to 100ms after it is excited, reaches full contraction about 0.5s later, and then declines in contractile force in another 1 - 2s, giving a total contraction time of 1-3s. ~ 30 x skeM. Total range 0.2 - 30s
2° to caused by the slowness of attachment and detachment of the cross- bridges
Max force of contraction
Often > SkeM
4 - 6 kg/cm2 for smoM
3 - 4 kg/cm2 for skeM
2° prolonged period of attachment of the myosin cross bridges to the actin filaments
Features of
prolonged holding of contractions e.g. hours
Little requirement for continuing excitation or further energy once muscle at full force of contraction
Little continued excitatory signal is required from nerve fibers or hormonal sources.
Theories of mechanisms
myosin heads tend to remain attached to actin despite a fall in cytoplasmic [Ca] and despite becoming phosphorylated
Stress- relaxation and reverse stress- relaxation.
visceral unitary type of smooth muscle of many hollow organs,
its ability to return to nearly its original force of contraction seconds or minutes after it has been elongated or shortened.
Occurs when ↑ and ↓ size of organ
Regulation of contraction by intraceullar [Ca2+] ions
↑ can be caused by:
nerve stimulation of the smooth muscle fiber,
hormonal stimulation,
stretch of the fiber,
changes in the chemical
Source of calcium ions that cause contraction
Tiny sarcoplasmic reticulum
Ca2+ enter from ECF .
[Ca2+] in the ECF is»_space;> [Ca2+] in ICF
rapid diffusion down conc gradient when calcium channels open in ~200 – 300ms. ‘latent period’ prior to contraction ~ 50x > skem.
force of contraction smoM highly dependent on [Ca2+] ECF.
A Calcium Pump Is Required to Cause Smooth Muscle Relaxation.
ATP dependent Ca2+ pump, pumps Ca2+ back into the ECF or into a SR, if it is present
requires ATP, is slow acting cf fast-acting sarcoplasmic reticulum pump in skeletal muscle.
Contributes to length of smoM contraction
Excitation-contraction coupling process
Activation
↑ the Ca2+ concentration in the cytosolic fluid 2°
Depolarization of the cell membrane with or without action potentials leads to the opening of voltage-gated Na+ and Ca2+ channels
Hormones and neurotransmitters may open ligand-gated (‘receptor- operated’) Ca2+ channels in the cell membrane.
The high levels of intracellular Ca++ cause release of more Ca++ from the sarcoplasmic reticulum (Ca++-induced Ca++ release). However most of the Ca2+ comes from the ECF
Ca2+ binds reversibly with calmodulin
The calmodulin- calcium complex then joins with and activates myosin light chain kinase (MLCK), activating it
MLCK, by phosphorylation, activates the myosin heads, which form cross-bridges between actin and myosin
The energy for phosphorylation comes from ATP.
The myosin head can now bind repetitively with the actin filament to perform cross bridge cycling
Excitation-contraction coupling process
Relaxation
Ca2+ channels close
Ca2+ pump transports Ca2+ ions out of cytosolic fluid
[Ca2+] intracelluarly falls below threshold concentration
de-phosphorylation of the myosin head by myosin phosphatase
Cycling stops
Contraction ceases
What is the role of nitric oxide (NO) in vascular smooth muscle?
It is produced continuously in vascular endothelium from L-arginine by the enzyme NO synthase.
It diffuses to the vascular smooth muscle cells and stimulates guanylate cyclase. cGTP –> cGMP –> activation of cGMP-dependent protein kinase (PKG),
Its effects are very localised because it is a highly reactive free radical with a short half-life (~6 seconds in blood)
is a major determinant of the basal resting tone of VSM in arterioles.
contributes to the thromboresistance of the vessel wall because of its inhibition of both platelet aggregation and platelet adhesion to the vessel wall.
What are some clinical examples of nitric oxide in smooth muscles?
Vascular shear stress
Blood flow can cause shear stress on endothelial cells –> stress contorts the endothelial cells –> significant ↑ in NO release –> NO then relaxes the blood vessels
Chronic vascular disease
When endothelial cells damaged by chronic hypertension / atherosclerosis, impaired NO synthesis may contribute to excessive vasoconstriction and worsening of the hypertension and endothelial damage. If untreated, this may eventually cause vascular injury and damage to vulnerable tissues such as the heart, kidneys, and brain.
NO to treat ischaemic pain
Before NO was discovered, clinicians used nitroglycerin, amyl nitrate, and other nitrate derivatives to treat patients who had angina pectoris
These drugs, when broken down chemically, release NO –> dilatation of vessels throughout the body
drugs (e.g., sildenafil) that inhibit cGMP- specific phosphodiesterase-5 (PDE-5), an enzyme that degrades cGMP.
By preventing the degradation of cGMP, the PDE- 5 inhibitors effectively prolong the actions of NO to cause vasodilation.
primary clinical use of the PDE- 5 inhibitors is to treat erectile dysfunction.
Penile erection is caused by parasympathetic nerve impulses through the pelvic nerves to the penis, where the neurotransmitters acetylcholine and NO are released. By preventing the degradation of NO, the PDE- 5 inhibitors enhance the dilation of the blood vessels in the penis and aid in erection.
