Physiology Ch 8 p91-98
Excitation and Contraction of Smooth Muscle
-Smooth muscle is composed of small fibers 1-5um in diameter and 20-500um in length
Types of Smooth Muscle – smooth muscle of each organ differs from other organs in physical
dimensions, organization into bundles or sheets, response to various stimuli, innervation, and
function
-can be characterized into multi-unit smooth muscle and unitary (single-unit) smooth muscle
Multi-unit smooth muscle – discrete/separate smooth muscle fibers acting independently and
each one is innervated by a single nerve ending, and is covered by layer of basement membrane
-each fiber can contract INDEPENDENTLY from one another, and are controlled mainly by
nerves, whereas unitary smooth muscle is usually non-nervous stimulation
-ciliary muscle of eye, iris, pilo-erector muscles of hair on skin
Unitary Smooth Muscle – also called syncytial smooth muscle or visceral smooth muscle
-all fibers contract together as a unit and are arranged in sheets or bundles joined by GAP
JUNCTIONS through which ions can freely flow so action potentials propagate
-called syncytial because of many interconnections, and called visceral because it is
often found in the visceral walls including GI, bile, ureters, uterus and vessels
Contractile Mechanism in Smooth Muscle
1. Chemical Basis for Smooth Muscle Contraction – contains both actin and myosin
filaments, but does not contain the normal troponin complex that is in skeletal muscle
a. Actin/myosin interact the same way as in skeletal muscle and the process is
activated by calcium and ATP degradation to ADP for energy
2. Physical Basis for Smooth Muscle Contraction – smooth muscle is not striated, but is
organized into large numbers of actin filaments attached to dense bodies, which are
attached to the cell membrane
a. Interspersed among actin filaments are myosin filaments which are 2x as wide
and 10x less prevalent
b. Large numbers of actin filaments project from the dense bodies which serve the
same role as Z-discs in skeletal muscle
c. Another difference is that most myosin filaments have sidepolar cross-bridges
arranged so that bridges on one side hinge in one direction and the other side
hinge on another direction, allowing them to pull actin in one direction while
simultaneously pulling another actin filament in the other direction. This allows
smooth muscle to contract as much as 80% of length instead of 30% (skeletal)
Comparison of Smooth Muscle and Skeletal Muscle Contraction
-most smooth muscle contraction is prolonged, lasting hours or days (skeletal is fast)
-smooth muscle cycles myosin cross-bridges very slowly (attachment and release to/from actin)
compared to skeletal muscle
-fraction of time that cross-bridges remain attached to actin filaments is increased in
smooth muscle
-slow cycling due to cross-bridge heads having less ATPase activity than skeletal muscle
-Low energy requirement to sustain smooth muscle contraction (1/10-1/300 that of skeletal),
due to slow attachment and detachment cycling of cross bridges and low ATPase activity
-Slowness of onset of contraction and relaxation of total smooth muscle tissue – typical smooth
muscle cell contracts 50-100m after excitation and reaches full contraction after 0.5s, which is
30x as long as skeletal muscle contraction, caused by slowness of attachment and detachment
of cross-bridges
-initiation of contraction in response to Ca ions is slower
-Maximum force of contraction is greater in smooth muscle than skeletal muscle – results from
prolonged attachment of myosin cross-bridges
-Latch mechanism facilitates prolonged holding of contractions of smooth muscle, where
amount of continuing excitation of fully contracted muscle doesn’t need to be as much as the
initial excitation, can maintain contraction in smooth muscle for hours
-Stress-relaxation of smooth muscle – important characteristic of smooth muscle that allows it
to return to full force of contraction seconds or minutes after it has been elongated or
shortened
-after urinary bladder stretching, the pressure on smooth muscle decreases back down
to normal after 15 seconds- 1 minute
-when volume decreases, pressure decreases, but then rises again rapidly
-maintains pressure
Regulation by Calcium Ions – initiating stimulus for both skeletal and smooth muscle is calcium
due to an increase in intracellular calcium due to nerve or hormonal stimulation, stretch of fiber,
or change in chemical environment
-smooth muscle does not contain troponin, so smooth muscle is activated differently
Calcium ions combine with calmodulin to cause activation of myosin kinase and
phosphorylatin of myosin head – instead of troponin, smooth muscle has calmodulin which is a
regulatory protein that activates myosin cross-bridges in the following sequence:
1. Ca binds calmodulin
2. Complex joins and activates myosin light chain kinase
3. Regulatory chain on each myosin head becomes phosphorylated by kinase, giving
the head the capability of binding repetitively with the actin filament and
proceeding through entire cycling process
Myosin Phosphatase Stops Contraction – when Ca ion concentration falls, the processes
reverse except for phosphorylation, which is reversed using a myosin phosphatase in cytosol of
smooth muscle cells, which causes the cycling to stop and ceases contraction
Possible mechanism for regulation of Latch phenomenon – when myosin kinase and myosin
phosphatase are both activated, cycling frequency is high. As activation decreases, cycling
decreases but the deactivation of these enzymes allows myosin heads to remain attached to
actin filament for a longer and longer proportion of cycling period
-therefore, number of heads attached to actin remains high, and tension is latched
Neuromuscular Junctions of Smooth Muscle – autonomic nerve fibers that innervate smooth
muscle branch diffusely on top of a sheet of muscle fibers, and do not usually make direct
contact with the smooth muscle cells but instead form diffuse junctions that secrete
neurotransmitters into matrix coating of smooth muscle a few nanometers away
-muscle excitation travels from outer layer to inner layers by action potential conduction
-axons do not have the typical end feet like in a motor end plate, but instead have multiple
varicosities distributed along their axes
-at this point, the schwann cells that envelope the axons are interrupted so that
substance can be secreted through the walls of varicosities
-vesicles of autonomic fibers sometimes contain acetylcholine, and other times contain
norepinephrine
-in multi-unit type smooth muscle, the varicosities are separated by 20-30nm from membrane,
which is the same width as synaptic cleft, and are called contact junctions, and function in the
same way as skeletal muscle neuromuscular junction
Excitatory and Inhibitory Transmitter Substances Secreted at Smooth Muscle Neuromuscular
Junction –
-acetylcholine is an excitatory neurotransmitter for smooth muscle of some organs but
inhibitory in others
-norepinephrine inhibits muscle that acetylcholine excites, and excites those that acetylcholine
inhibits
-this is accomplished by both of these binding to respective receptors on cell surface, which can
either be excitatory or inhibitory
Membrane potentials and Action Potentials in smooth muscle
-the normal resting state potential is usually -50 to -60mV, 30 less negative than skeletal muscle
-action potentials occur in unitary smooth muscle the same way as in skeletal muscle, but do not
occur in multi-unit muscle, and they occur in two forms (1) spike potentials and (2) action
potentials with plateaus
Spike Potentials – typical spike potentials occur in unitary smooth muscle, last 10-50ms, and can
be elicited by electrical stimulation, hormone action on smooth muscle, neurotransmitters,
stretch, or spontaneous generation
Action Potentials with Plateaus – onset of action potential is similar to spike potential, but a
rapid repolarization does not occur, and is delayed several hundred to 1000ms, and is important
in prolonged contraction in muscles such as ureter
Calcium Channels important in generating smooth muscle action potential – smooth muscle
has much more voltage-gated Ca channels, but few Na channels, so Na does not contribute as
much as Ca
-Ca channels open much more slowly than Na channels and remain open longer, causing large
plateau potentials, and Ca acts directly on contractile machinery to cause contraction
Slow wave potentials in unitary smooth muscle can lead to spontaneous generation of action
potentials – some smooth muscle is self-excitatory, and has a basic slow wave rhythm of
membrane, which is not an action potential, caused by waxing and waning of pumping positive
ions outward through muscle fiber membrane
-when slow waves are strong enough, they can initiate action potentials, but they themselves
cannot contract muscle, and can only make resting membrane potential less negative
-slow waves are called pacemaker waves
Excitation of Visceral Smooth Muscle by Muscle Stretch – when unitary smooth muscle is
stretched, spontaneous action potentials occur resulting from normal slow wave potentials and
decrease in overall negativity of membrane potential caused by stretch itself
Depolarization of Multi-unit smooth muscle without action potentials – these fibers contract
mainly in response to nerve stimuli, which secrete acetylcholine and norepinephrine depending
on where the muscle is, which cause depolarization of membrane to contract muscle
-action potentials DO NOT DEVELOP, because fibers are too small to generate action potential
-local depolarization (junctional potential) can spread over entire fiber to cause contraction
Effect of Local Tissue Factors and Hormones to Cause Contraction – 50% of all smooth muscle
contraction is caused by factors such as tissue factors and hormones
Tissue Factors – relates to control of contraction of arterioles, and precapillary sphincters.
Factors can relax vessel walls to increase flow, providing for a local feedback control system,
some factors are:
1. lack of O2 in local tissues causes vascular smooth muscle relaxation (vasodilation)
2. Excess CO2 causes vasodilation
3. Increased H+ concentration causes vasodilation
-Adenosine, lactic acid, increased K+, less Ca, and increased temp increases vasodilation
Hormones – norepinephrine, epinephrine, acetylcholine, angiotensin, endothelin, vasopressin,
oxytocin, serotonin, histamine
-a hormone causes contraction when cell has excitatory receptor for that hormone, and
can cause inhibition of contraction when cell has inhibitory receptor
Mechanism of Smooth Muscle Excitation of Inhibition by Hormones and Local Tissue Factors –
some hormone receptors in smooth muscle membrane open Na or Ca ion channels and
depolarize membrane. Sometimes action potentials result or are enhanced
-inhibition occurs when hormone closes Na or Ca channels to prevent entry of positive ions
-inhibition also occurs if normally closed K+ channels are opened to result in hyperpolarization
-sometimes a hormone can regulate contraction without changing membrane potential, but
does so by causing change in muscle fiber such as release of Ca from sarcoplasmic reticulum to
induce it
-to inhibit contraction, other receptor mechanisms activate adenylyl cyclase or guanylyl
cyclase in the cell membrane to create cAMP or cGMP to change degree of
phosphorylation of several enzymes that indirectly inhibit contraction
-norepinephrine inhibits contraction of smooth muscle in the intestine but stimulates
contraction in blood vessels
Source of Ca ions that cause contraction through cell membrane and from sarcoplasmic
reticulum – sarcoplasmic reticulum is only partially developed in smooth muscle, and most of
the Ca comes from extracellular fluid at the time of stimulus or action potential
-time for diffusion to occur lasts 200-300ms and is called the latency period before contraction
Role of Smooth Muscle Sarcoplasmic Reticulum – small invaginations called caveolae in cell
membrane receive action potentials and believed to excite Ca ion release from abutting
sarcoplasmic tubules… the more extensive the sarcoplasmic reticulum is, the faster contraction
Smooth Muscle Contraction Dependent on Extracellular Ca – when extracellular Ca falls to 1/3
to 1/10 of normal, smooth muscle contraction ceases, therefore the force of contraction
depends on extracellular fluid calcium
A Ca pump is required to cause smooth muscle relaxation – to cause smooth muscle relaxation,
Ca ions must be moved from intracellular fluids, achieved by calcium pump that pumps Ca ions
out of smooth muscle back into extracellular fluid or sarcoplasmic reticulum
-slow acting compared to that of skeletal muscle, causing prolonged contraction