Smooth Muscle Physiology

***** Myosin of the thick filaments of smooth muscle is only able to bind to actin when it is x. Increased intracellular Ca2+ in smooth muscle leads to the x of myosin by the following steps (FIGURE 5). a) Ca2+ binds to x within the smooth muscle fiber. b) The Ca2+-calmodulin complex binds to and activates x; activation is due to x of MLCK). c) The activated myosin kinase then phosphorylates x. d) Phosphorylated myosin of the smooth muscle x filaments binds to actin of the thin filaments allowing cross-bridge cycling and contraction. The process is generally much x than in skeletal or cardiac muscle. 2+ e) Relaxation of smooth muscle is accomplished by moving Ca back into the 2+ extracellular fluid across the surface membrane, and by active pumping of x into the SR (see also autonomic nervous system effects on smooth muscle below). f) Smooth muscle usually contracts and relaxes much more x than skeletal muscle, with single contractions lasting as long as several seconds. Myosin ATPase of smooth muscle splits ATP at a much slower rate than in skeletal muscle, resulting in x. Nevertheless, in comparison to skeletal muscle, smooth muscle is capable of generating as much (or more) x per unit of cross sectional area.

***** Myosin of the thick filaments of smooth muscle is only able to bind to actin when it is phosphorylated. Increased intracellular Ca2+ in smooth muscle leads to the phosphorylation of myosin by the following steps (FIGURE 5). a) Ca2+ binds to calmodulin within the smooth muscle fiber. b) The Ca2+-calmodulin complex binds to and activates myosin kinase (myosin light chain-kinase, MLCK; activation is due to de-phosphorylation of MLCK). c) The activated myosin kinase then phosphorylates myosin. d) Phosphorylated myosin of the smooth muscle thick filaments binds to actin of the thin filaments allowing cross-bridge cycling and contraction. The process is generally much slower than in skeletal or cardiac muscle. 2+ e) Relaxation of smooth muscle is accomplished by moving Ca back into the 2+ extracellular fluid across the surface membrane, and by active pumping of Ca back into the SR (see also autonomic nervous system effects on smooth muscle below). f) Smooth muscle usually contracts and relaxes much more slowly than skeletal muscle, with single contractions lasting as long as several seconds. Myosin ATPase of smooth muscle splits ATP at a much slower rate than in skeletal muscle, resulting in slower cross-bridge cycling. Nevertheless, in comparison to skeletal muscle, smooth muscle is capable of generating as much (or more) tension per unit of cross sectional area.

*Length-Tension Relationship in Smooth Muscle: a) In a limited sense, the length-tension relationship for smooth muscle is qualitatively similar to that of skeletal and cardiac muscle, i.e., there is a range (relatively broad) of lengths where tension development is at or near its maximum. At both shorter and longer lengths active tension x. b) However, smooth muscle is capable of x to about x of its 'resting' length and can still develop tension when it has been stretched to about x times its resting length. Thus, smooth muscle can generate tension over a x-fold variation in length. This can be contrasted with skeletal muscle, which normally operates only within 70-130% of its resting length. c) The ability of smooth muscle to develop tension over this wide range of lengths is important to its functional role in the body. The hollow organs, which are surrounded by smooth muscle, can often vary in diameter a great deal (for example, consider the urinary bladder), yet smooth muscle remains able to generate active tension over the entire usual range of muscle fiber lengths. d) Because the contractile behavior of smooth muscle is so highly dependent on x influences, there is no meaningful and unique length-tension or force-velocity relationship for some types of smooth muscle in their physiological situation within the body.

*Length-Tension Relationship in Smooth Muscle: a) In a limited sense, the length-tension relationship for smooth muscle is qualitatively similar to that of skeletal and cardiac muscle, i.e., there is a range (relatively broad) of lengths where tension development is at or near its maximum. At both shorter and longer lengths active tension declines. b) However, smooth muscle is capable of shortening to about 1/2 of its 'resting' length and can still develop tension when it has been stretched to about 2.5 times its resting length. Thus, smooth muscle can generate tension over a 5-fold variation in length. This can be contrasted with skeletal muscle, which normally operates only within 70-130% of its resting length. c) The ability of smooth muscle to develop tension over this wide range of lengths is important to its functional role in the body. The hollow organs, which are surrounded by smooth muscle, can often vary in diameter a great deal (for example, consider the urinary bladder), yet smooth muscle remains able to generate active tension over the entire usual range of muscle fiber lengths. d) Because the contractile behavior of smooth muscle is so highly dependent on external influences, there is no meaningful and unique length-tension or force-velocity relationship for some types of smooth muscle in their physiological situation within the body.

***Smooth muscle contraction 1. Increase in cytosolic [Ca2+]. 2. Ca2+ binds to calmodulin (Ca2+ -binding protein) in cytosol. 3. Ca-calmodulin complex binds to and activates the enzyme myosin light-chain kinase (MLCK). 4. MLCK uses ATP to x cross-bridges. 5. Phosphorylated myosin forms cross-bridges with actin filaments. 6. Cross-bridge cycle produces tension and shortening. 7. Power stroke is the x from myosin head. 8. Cross-bridge detachment requires x.

1. Increase in cytosolic [Ca2+]. 2. Ca2+ binds to calmodulin (Ca2+ -binding protein) in cytosol. 3. Ca-calmodulin complex binds to and activates the enzyme myosin light-chain kinase (MLCK). 4. MLCK uses ATP to phosphorylate myosin cross-bridges. 5. Phosphorylated myosin forms cross-bridges with actin filaments. 6. Cross-bridge cycle produces tension and shortening. 7. Power stroke - release of ADP-Pi from myosin head. 8. Cross-bridge detachment requires ATP.

*Four major different ways of producing contraction in smooth muscle and places you'd expect to see these mechanisms

1. Twitch, summation in vascular smooth muscles 2. Chronic depolarization or hyperpolarization in vascular SM 3. Slow waves with AP bursts at wave crests - in GI 4. Contractile activity in the absence of electrical activity i.e pharmacomechanical coupling - not specifically one area in particular.

Name three different types of smooth muscle arrangement

1. circular layer of an arteriole 2. circular (below) and longitudinal layers (above) of intestinal wall 3. rectangular smooth muscle of a small testicular duct

Functional roles of smooth muscle contraction: propels contents through a hollow organ or tube. maintains pressure against the contents within a hollow organ or tube. regulates internal flow of contents by changing tube diameter (resistance). What role would you expect to have? 1. circular layer in arterioles, airways 2. rectangular layer in bladder,rectum, small testicular duct 3. circular and longitudinal layers in intestinal wall

1. maintain pressure 2. regulates internal flow 3. mix and propel contents

Two major types of smooth muscle based on electrical coupling between fibers

1. single-unit 2. multi-unit There are also tonic and phasic varieties

1. Although smooth muscle cells contain thick myosin filaments and thin actin filaments, the contractile elements (and cytoskeletal elements) are not x as they are in striated (skeletal and cardiac) muscle. 2. This lack of striations results in an apparent x in light and electron micrographs of smooth muscle cells, which in the past has sometimes led to the conclusion that smooth muscle is more poorly developed than skeletal and cardiac muscle. However, smooth muscle is highly specialized for its role in the body. The organization of its contractile apparatus remains less well understood than that of striated muscle, but this may simply reflect the need for improved 3 D imaging techniques.

Although smooth muscle cells contain thick myosin filaments and thin actin filaments, the contractile elements (and cytoskeletal elements) are not arranged transversely as they are in striated (skeletal and cardiac) muscle. This lack of striations results in an apparent lack of organization in light and electron micrographs of smooth muscle cells, which in the past has sometimes led to the conclusion that smooth muscle is more poorly developed than skeletal and cardiac muscle. However, smooth muscle is highly specialized for its role in the body. The organization of its contractile apparatus remains less well understood than that of striated muscle, but this may simply reflect the need for improved 3 D imaging techniques.

*****As already described, single-unit smooth muscle often displays spontaneous activity. A variety of factors can modify the contractile activity of smooth muscle. These include: 3.9.1 Autonomic neurotransmitters. Smooth muscle typically receives innervation from both the sympathetic and parasympathetic branches of the autonomic nervous system (there are exceptions: e.g., vascular smooth muscle generally receives only x innervation). For x-unit smooth muscle, such innervation does not normally initiate contraction, but it can modify both the rate of activity and the strength of contraction. Autonomic nervous system axons do not x with the single-unit smooth muscle cells in the way you are familiar with at the neuromuscular junction in skeletal muscle. x and x receptors are dispersed over the entire surface of the smooth muscle cells. The postganglionic autonomic fibers travel across the surface of smooth muscle cells. Varicosities in the axon terminal release x that diffuses to receptor sites on the muscle cells (FIGURE 8A). Thus, smooth muscle cells can be influenced by more than one type of transmitter.

As already described, single-unit smooth muscle often displays spontaneous activity. A variety of factors can modify the contractile activity of smooth muscle. These include: 3.9.1 Autonomic neurotransmitters. Smooth muscle typically receives innervation from both the sympathetic and parasympathetic branches of the autonomic nervous system (there are exceptions: e.g., vascular smooth muscle generally receives only sympathetic innervation). For single-unit smooth muscle, such innervation does not normally initiate contraction, but it can modify both the rate of activity and the strength of contraction. Autonomic nervous system axons do not synapse with the single-unit smooth muscle cells in the way you are familiar with at the neuromuscular junction in skeletal muscle. Adrenergic and cholinergic receptors are dispersed over the entire surface of the smooth muscle cells. The postganglionic autonomic fibers travel across the surface of smooth muscle cells. Varicosities in the axon terminal release transmitter that diffuses to receptor sites on the muscle cells (FIGURE 8A). Thus, smooth muscle cells can be influenced by more than one type of transmitter.

*As is the case in striated muscle, increased x concentration is an important trigger for contraction in smooth muscle cells. 2. Most of this Ca2+ enters from the extracellular fluid across the cell membrane through: Voltage-gated Ca2+ channels, ligand (second messenger)-gated Ca2+ channels, receptor- gated Ca2+ channels, x-activated Ca2+ channels. Some Ca2+ is also released intracellularly from the SR; however, the SR in smooth muscle is x. 3. The x of smooth muscle cells makes Ca2+ diffusion from the surface to the center of the fiber a relatively fast process. 4. Ca x induced Ca2+ release or via x (with elevated levels due to the activation of G-protein coupled receptors).

As is the case in striated muscle, increased myoplasmic Ca concentration is an important trigger for contraction in smooth muscle cells. Most of this Ca2+ enters from the extracellular fluid across the cell membrane through: Voltage-gated Ca2+ channels, ligand (second messenger)-gated Ca2+ channels, receptor- gated Ca2+ channels, stretch-activated Ca2+ channels. Some Ca2+ is also released intracellularly from the SR; however, the SR in smooth muscle is relatively poorly developed. The small diameter of smooth muscle cells makes 2+ diffusion from the surface to the center of the fiber a relatively fast process. Ca release from the SR can be either by Ca2+ induced Ca2+ release or via IP3 (with elevated levels due to the activation of G-protein coupled receptors).

*****Electrical Activity of Smooth Muscle. Smooth muscle cells generally have low resting potentials in the range of x to x mV. Single-unit smooth muscle is electrically coupled by gap junctions. Gap junctions are much less common in multiunit smooth muscle. Many (but not all) types of single-unit smooth muscle are x, i.e., groups of specialized smooth muscle cells in this tissue generate spontaneous electrical activity that can then spread to other cells via gap junctions. The two most common types of spontaneous depolarizations are: a) x activity, in which the membrane potential gradually and spontaneously changes because of shifting patterns of membrane x. In many respects this is similar to pacemaker activity already described in the heart. When the membrane potential reaches threshold, an action potential is generated. After the action potential, the membrane potential once again begins to depolarize. See FIGURE 6. The spontaneous depolarization results from the activation of a small cationic current (mostly x). b) x potentials are the other form of spontaneous electrical behavior (FIGURE 6 right). These are alternating gradual hyperpolarizing and depolarizing swings of membrane potential that are thought to result from spontaneous cyclical changes in the rate of x across the membrane. Slow wave potentials may or may not lead to action potentials. If the potential rises above threshold, x action potentials often result. Not all smooth muscle cells generate action potentials. In any case, action potentials are not always required to generate contraction (see below). Smooth muscle cells contain voltage-sensitive x channels, which are opened by membrane depolarization. Some smooth muscle cells apparently also contain receptor-activated Ca2+ channels, which require binding of specific substances to receptors to open.

Electrical Activity of Smooth Muscle. Smooth muscle cells generally have low resting potentials in the range of -50 to -70 mV. Single-unit smooth muscle is electrically coupled by gap junctions. Gap junctions are much less common in multiunit smooth muscle. Many (but not all) types of single-unit smooth muscle are self-excitable, i.e., groups of specialized smooth muscle cells in this tissue generate spontaneous electrical activity that can then spread to other cells via gap junctions. The two most common types of spontaneous depolarizations are: a) Pacemaker activity, in which the membrane potential gradually and spontaneously changes because of shifting patterns of membrane permeability. In many respects this is similar to pacemaker activity already described in the heart. When the membrane potential reaches threshold, an action potential is generated. After the action potential, the membrane potential once again begins to depolarize. See FIGURE 6. The spontaneous depolarization results from the activation of a small cationic current (mostly Na+). b) Slow-wave potentials are the other form of spontaneous electrical behavior (FIGURE 6 right). These are alternating gradual hyperpolarizing and depolarizing swings of membrane potential that are thought to result from spontaneous cyclical + changes in the rate of active transport of (in many cases) Na across the membrane. Slow wave potentials may or may not lead to action potentials. If the potential rises above threshold, bursts of several action potentials often result. Not all smooth muscle cells generate action potentials. In any case, action potentials are not always required to generate contraction (see below). Smooth muscle cells contain voltage-sensitive Ca2+ channels, which are opened by membrane depolarization. Some smooth muscle cells apparently also contain receptor-activated Ca2+ channels, which require binding of specific substances to receptors to open.

Examples of x smooth muscle occur in the gastrointestinal, reproductive and urinary systems. x smooth muscle usually produces action potentials; these either initiate contraction, or increase the contractile response.

Examples of phasic smooth muscle occur in the gastrointestinal, reproductive and urinary systems. Phasic smooth muscle usually produces action potentials; these either initiate contraction, or increase the contractile response.

Phasic smooth muscle usually produces action potentials; these either initiate contraction, or increase the X.

Examples of phasic smooth muscle occur in the gastrointestinal, reproductive and urinary systems. Phasic smooth muscle usually produces action potentials; these either initiate contraction, or increase the contractile response.

Factors can influence the contraction of SM by changing the permeability to Ca2+ of the X and/or the X.

Factors can influence the contraction of SM by changing the permeability to Ca2+ of the surface membrane and/or the SR.

T/F - Unlike skeletal muscle, smooth muscle does not have troponin, t-tubules, or SR

False - smooth muscle DOES NOT have troponin or t-tubules, but it does have some SR, but less developed than in skeletal muscle

Functional roles of smooth muscle contraction: X contents through a hollow organ or tube. maintains X against the contents within a hollow organ or tube. regulates internal flow of contents by changing tube X (resistance).

Functional roles of smooth muscle contraction: propels contents through a hollow organ or tube. maintains pressure against the contents within a hollow organ or tube. regulates internal flow of contents by changing tube diameter (resistance).

You give your patient a drug that is an α2 adrenergic receptor agonist. What will be the effect on blood pressure?

Go up - α2 adrenergic receptor activation causes vasoconstriction.

Many smooth muscle cells (mostly of the x type) can maintain a low level of tension (tone) even in the absence of electrical activity, and apparently without elevated x concentration.

Many smooth muscle cells (mostly of the single unit type) can maintain a low level of tension (tone) even in the absence of electrical activity, and apparently without elevated myoplasmic Ca2+ concentration.

Rate limiting step for smooth muscle contraction

Myosin ATP-ase action -crossbridge formation

Note that smooth muscle also contains structures called x, which take the place of Z lines in striated muscle in that they anchor the thin filaments. x contain many of the same proteins found in Z lines of striated muscle. x are essentially dense bodies that are associated with the sarcolemma and are involved in mechanical coupling between neighboring cells. Smooth muscle cells are mechanically coupled, and to varying degrees (see below) x coupled.

Note that smooth muscle also contains structures called dense bodies, which take the place of Z lines in striated muscle in that they anchor the thin filaments. Dense bodies contain many of the same proteins found in Z lines of striated muscle. Dense areas are essentially dense bodies that are associated with the sarcolemma and are involved in mechanical coupling between neighboring cells. Smooth muscle cells are mechanically coupled, and to varying degrees (see below) electrically coupled.

Besides ß2, α1, α2 adrenergic receptors, what other factors can influence the contraction of both single-unit and multi-unit smooth muscle? How do they do it?

Other factors will influence the contraction of both single-unit and multi-unit smooth 2+ muscle by changing the permeability to Ca of the surface membrane and/or the SR: Hormones: histamine, serotonin, vasopressin, oxytocin, angiotensin, substance P, gastric hormones (gastrin, cholecystokinin, secretin, motilin, neurotensin). Mechanical stretch Local metabolites: CO2, lactic acid, ADP. Drugs: Many clinically relevant drugs affect excitation-contraction coupling (or other contractile mechanisms) in vascular smooth muscle cells. These drugs can be used to treat hypertension. Ca2+ antagonists. These drugs block voltage-dependent Ca2+ channels, reducing Ca2+ influx and Ca2+ -induced Ca2+ release. Examples: nifedipine, verapamil, diltiazem. K+ channel openers. These drugs cause hyperpolarization of smooth muscle cells. Hyperpolarization decreases Ca2+ influx through voltage-dependent Ca2+ channels and promotes relaxation of smooth muscle and vasodilation of peripheral blood vessels. Example: pinacidil. Nitric oxide/cyclicGMP stimulators. Many vasodilators produce nitric oxide (NO) or otherwise stimulate the nitric oxide-cyclic GMP pathway, resulting in elevated cGMP concentrations in the cytosol. cGMP relaxes smooth muscle. Example: NO donors such as nitroglycerin.

The two major types of spontaneous excitation in smooth muscle cells. Would these SM cells be single or multi unit?

Pacemaker activity and slow-wave potentials. Also, most common in single-unit SM

***Explain the factors that would contribute to the rise and fall of a slow wave potential.

Rise 1. v-gated Ca2+ channels open due to spontaneous depolarization 2. Ca2+ influx, binds to calmodulin 3. Ca-Calmodulin binds MLCK, which then phosphorylates myosin and triggers crossbridge formation Fall 1. Upon depolarization, Ca2+ K+ channels open and slowly repolarize 2. As Vm goes more negative, V-gated Ca2+ channels close and decrease intracellular Ca2+ 3. Lack of intracellular Ca2+ causes closure of Ca2+ activated K+ channels.

SM pattern of innervation 1. x innervation - derived from the ANS (arteries) 2. x nerves contained in plexuses (GI Tract) 3. x neurons - mediate various reflexes (plexus)

SM pattern of innervation 1. Extrinsic innervation - derived from the ANS (arteries) 2. Intrinsic nerves contained in plexuses (GI Tract) 3. Afferent sensory neurons - mediate various reflexes (plexus)

Differentiate between single-unit smooth muscle and multi-unit smooth muscle.

Single-unit smooth muscle is the most common type. The fibers of single unit smooth muscle are electrically coupled by gap junctions so that they become excited and contract as a single unit. Single unit smooth muscle is sometimes called visceral smooth muscle because it is typical of visceral organs, including the walls of the gastrointestinal tract, the reproductive and urinary tracts and the smooth muscle of small blood vessels. Single-unit smooth muscle does not require nervous system stimulation to contract. Instead, it is self-excitable, with groups of fibers within single-unit smooth muscle producing spontaneous activity (although activity may often be modulated by the autonomic nervous system and other factors). 3.3.2 Multi-unit smooth muscle contains relatively few gap junctions. Thus at most only a small number of neighboring cells act as a unit. The multiple discrete units of this type of smooth muscle act independently and must be separately stimulated by nerves to contract. Multiunit smooth muscle is found in the walls of larger blood vessels, the iris of the eye, the airways of the lungs, and in the skin surrounding hair follicles. The distinction between single-unit and multi-unit smooth muscle is an over-simplification, and becomes difficult to separate in some tissues.

Which is single unit SM or multi-unit SM? 1. most common type. 2. electrically coupled by gap junctions so that they become excited and contract as a single unit. 3. sometimes called visceral smooth muscle because it is typical of visceral organs, including the walls of the gastrointestinal tract, the reproductive and urinary tracts and the smooth muscle of small blood vessels. 4. does not require nervous system stimulation to contract. Instead, it is self-excitable, with groups of fibers within single-unit smooth muscle producing spontaneous activity (although activity may often be modulated by the autonomic nervous system and other factors). 5. contains relatively few gap junctions. Thus at most only a small number of neighboring cells act as a unit. 6. The multiple discrete units of this type of smooth muscle act independently and must be separately stimulated by nerves to contract. 7. is found in the walls of larger blood vessels, the iris of the eye, the airways of the lungs, and in the skin surrounding hair follicles. 8. The distinction between single-unit and multi-unit smooth muscle is an over-simplification, and becomes difficult to separate in some tissues.

Single-unit smooth muscle is the most common type. The fibers of single unit smooth muscle are electrically coupled by gap junctions so that they become excited and contract as a single unit. Single unit smooth muscle is sometimes called visceral smooth muscle because it is typical of visceral organs, including the walls of the gastrointestinal tract, the reproductive and urinary tracts and the smooth muscle of small blood vessels. Single-unit smooth muscle does not require nervous system stimulation to contract. Instead, it is self-excitable, with groups of fibers within single-unit smooth muscle producing spontaneous activity (although activity may often be modulated by the autonomic nervous system and other factors). 3.3.2 Multi-unit smooth muscle contains relatively few gap junctions. Thus at most only a small number of neighboring cells act as a unit. The multiple discrete units of this type of smooth muscle act independently and must be separately stimulated by nerves to contract. Multiunit smooth muscle is found in the walls of larger blood vessels, the iris of the eye, the airways of the lungs, and in the skin surrounding hair follicles. The distinction between single-unit and multi-unit smooth muscle is an over-simplification, and becomes difficult to separate in some tissues.

1. Smooth muscle cells are x shaped and are much larger/smaller than skeletal muscle cells. They are about 2-10 microns in diameter and about 50 to 400 microns long. Smooth muscle cells do NOT have a x system. They do have sarcoplasmic reticulum, but it is much more x developed than in skeletal or cardiac muscle. Smooth muscle cells do not x of the whole muscle (unlike skeletal muscle, but like cardiac muscle). Typically smooth muscle cells are arranged in x (FIGURE 1).

Smooth muscle cells are spindle shaped and are much smaller than skeletal muscle cells. They are about 2-10 microns in diameter and about 50 to 400 microns long. Smooth muscle cells do NOT have a transverse tubular system. They do have sarcoplasmic reticulum, but it is much more poorly developed than in skeletal or cardiac muscle. Smooth muscle cells do not extend the entire length of the whole muscle (unlike skeletal muscle, but like cardiac muscle). Typically smooth muscle cells are arranged in sheets (FIGURE 1).

Smooth muscle cells contain three types of filaments: 1. Thick x filaments are longer than those in skeletal muscle. 2. Thin x filaments. Unlike skeletal and cardiac muscle these filaments DO NOT contain x and x (although they do contain proteins called calponin and caldesmon that may serve regulatory roles). Relative to striated muscle, thin filaments are more x in smooth muscle (about 10 thin filaments per thick filament, versus 2 sets of thin filaments per thick filament in striated muscle). The thin filaments of smooth muscle are also x than those of striated 3. Intermediate filaments. These are not contractile elements, but instead are part of the cell's cytoskeleton and are probably responsible for some of the x properties of smooth muscle.

Smooth muscle cells contain three types of filaments: 3.2.1 Thick myosin filaments are longer than those in skeletal muscle. 3.2.2 Thin actin filaments. Unlike skeletal and cardiac muscle these filaments DO NOT contain troponin and tropomyosin (although they do contain proteins called calponin and caldesmon that may serve regulatory roles). Relative to striated muscle, thin filaments are more numerous in smooth muscle (about 10 thin filaments per thick filament, versus 2 sets of thin filaments per thick filament in striated muscle). The thin filaments of smooth muscle are also longer than those of striated muscle. 3.2.3 Intermediate filaments. These are not contractile elements, but instead are part of the cell's cytoskeleton and are probably responsible for some of the elastic properties of smooth muscle.

Smooth muscle is found in the walls of the hollow internal organs, including all blood vessels except the capillaries, the gastrointestinal tract, and the urinary bladder. Smooth muscle is not X and it is not subject to X control.

Smooth muscle is found in the walls of the hollow internal organs, including all blood vessels except the capillaries, the gastrointestinal tract, and the urinary bladder. Smooth muscle is not striated and it is not subject to voluntary control.

Tone (continuous partial contraction) of tonic smooth muscle is not associated with X, although it is affected by membrane potential. 2. Recent evidence indicates that in tonic smooth muscle resting tone is usually dependent/not dependent on elevated myoplasmic Ca2+ concentration

Tone (continuous partial contraction) of tonic smooth muscle is not associated with action potentials, although it is affected by membrane potential. Recent evidence indicates that in tonic smooth muscle resting tone is usually NOT dependent on elevated myoplasmic Ca2+ concentration

Tonic smooth muscles are muscles that are partially active all the time; examples include smooth muscle in the walls of most blood vessels, the airways of the lungs and various sphincters, all of which maintain a continuous level of partial contraction that is called x.

Tonic smooth muscles are muscles that are partially active all the time; examples include smooth muscle in the walls of most blood vessels, the airways of the lungs and various sphincters, all of which maintain a continuous level of partial contraction that is called tone.

x smooth muscles are muscles that are partially active all the time; examples include smooth muscle in the walls of most blood vessels, the airways of the lungs and various sphincters, all of which maintain a continuous level of partial contraction that is called tone.

Tonic smooth muscles are muscles that are partially active all the time; examples include smooth muscle in the walls of most blood vessels, the airways of the lungs and various sphincters, all of which maintain a continuous level of partial contraction that is called tone.

Four major ways to produce SM contraction 1. Triggered action potentials open voltage-sensitive Ca2+ channels in the cell membrane to generate x x tension (FIGURE 7A). 2. x potential changes can trigger action potentials, leading to contraction. Slow-wave activity is associated with action potentials (FIGURE 7B). 3. Slow oscillations in potential (sometimes reflecting changes in the activity of x) can cause changes in tonic contractile activity in the absence of x (FIGURE 7C). Smooth muscle cells also show x coupling in which changes of tension development are caused by drugs or hormones. Sometimes this can occur in the absence of significant changes in x

Triggered action potentials open voltage-sensitive Ca2+ channels in the cell membrane to generate slow summating tension (FIGURE 7A). Spontaneous potential changes can trigger action potentials, leading to contraction. Slow-wave activity is associated with action potentials (FIGURE 7B). Slow oscillations in potential (sometimes reflecting changes in the activity of electrogenic pumps) can cause changes in tonic contractile activity in the absence of action potentials (FIGURE 7C). Smooth muscle cells also show pharmacomechanical coupling in which changes of tension development are caused by drugs or hormones. Sometimes this can occur in the absence of significant changes in membrane potential

The dense bodies of smooth muscle are analogous to x in skeletal and cardiac muscle

Z-lines

Smooth muscle does not have troponin or tropomyosin, but it does have two regulatory proteins called x and x

calponin and caldesmon

T/F - Smooth muscle has myofibrils

false

T/F - The myosin ATPase of smooth muscle is faster than in skeletal muscle

false

T/F- Smooth muscle cannot switch from being multi unit or single unit

false - uterus SM goes from being multiunit to single unit in order to contract uniformly during labor.

histamine, serotonin, vasopressin, oxytocin, angiotensin, substance P, gastrin, cholecystokinin, secretin, motilin, neurotensin ARE ALL EXAMPLES OF

hormones that can regulate SM contraction

What would be the effect of a K+ channel opener on SM?

hyperpolarization - decreases Ca2+ influx through v-dependent Ca2+ channels and promotes relaxation of SM and vasodilation.

increased cytoplasmic cAMP increases/decreases smooth muscle contraction but increases/decreases contraction of the heart.

increased cytoplasmic cAMP decreases smooth muscle contraction but increases contraction of the heart.

Would you expect single or multi unit smooth muscle to have more varicosities?

multi unit

Varicosity

periodic bulges in axon that release synaptic vesicles

Muscles that do not maintain resting tone, but instead contract rhythmically or intermittently.

phasic smooth muscles

Calponin and caldesmon

possible regulatory proteins in smooth muscle in place of troponin and tropomyosin

These are alternating gradual hyperpolarizing and depolarizing swings of membrane potential that are thought to result from spontaneous cyclical changes in the rate of active transport of (in many cases) Na across the membrane.

slow-wave potentials

T/F - Smooth muscle does not have sarcomeres

true

T/F - Though myosin ATPase of smooth muscle splits ATP at a much slower rate than in skeletal muscle, smooth muscle is capable of generating as much tension / more tension than skeletal muscle

true

T/F - smooth muscle cells can be influenced by more than one type of neurotransmitter.

true

Activation of ß2 adrenergic receptors in arteriolar smooth muscle will cause relaxation or constriction? Is there any other area of the body where a different effect would be observed?

ß2 activation in arteriolar smooth muscle will cause relaxation and vasodilation - due to GPCR cascade that activates PKA, which phosphorylates and inactivates MLCK. In the heart, ß2 activation leads to elevated cAMP and PKA, which opens several channels like the SR Ca2+ pump - leading to increased force of contraction.

Give 3 examples of pharmacomechanical coupling and their effects

ß2 adrenergic receptors - vasodilate α1 and α2 adrenergic - vasoconstrict

α1 adrenergic receptors 1. couple to x via G-proteins. 2. PLC catalyzes the hydrolysis of x to IP3 and DAG. 3. IP3 diffuses within the cell to ER and SR and causes x. 4. In smooth muscle IP3 binds to a channel in the SR membrane known as x that is a member of the same 'super-family' as the ryanodine receptor (i.e., the SR Ca2+ release channel). This channel is ligand-gated (must bind specific substances to open), and is opened when it binds IP3. 5. The resulting Ca2+ release from the SR causes the smooth muscle to x. Once again, this need not involve any change in the membrane potential of the smooth muscle cell; it is another example of pharmacomechanical coupling.

α1 adrenergic receptors couple to phospholipase C (PLC) via G-proteins. PLC catalyzes the hydrolysis of PIP2 to IP3 and DAG. IP3 diffuses within the cell to ER and SR and causes Ca2+ release. In smooth muscle IP3 binds to a channel in the SR membrane (IP3R) that is a member of the same 'super-family' as the ryanodine receptor (i.e., the SR Ca2+ release channel). This channel is ligand-gated (must bind specific substances to open), and is opened when it binds IP3. The resulting Ca2+ release from the SR causes the smooth muscle to contract. Once again, this need not involve any change in the membrane potential of the smooth muscle cell; it is another example of pharmacomechanical coupling.

α2 adrenergic receptors 1. have the opposite effect as x receptors. 2. They work through a G-protein with an inhibitory α subunit causing x of adenylyl cyclase, which results in decreased myoplasmic levels of cAMP. 3. In arteriolar smooth muscle this leads to dephosphorylation and activation of x. 4. Activated myosin kinase phosphorylates myosin of smooth muscle thick filaments causing contraction. The arterioles will x. 5. Once again, this pathway need not involve any change in the x of the smooth muscle cell. Moreover, it does not need to involve changes in cytoplasmic x concentration.

α2 adrenergic receptors 1. have the opposite effect as ß2 adrenergic receptors.. They work through a G-protein with an inhibitory α subunit causing inhibition of adenylyl cyclase, which results in decreased myoplasmic levels of cAMP. In arteriolar smooth muscle this leads to dephosphorylation and activation of myosin kinase. Activated myosin kinase phosphorylates myosin of smooth muscle thick filaments causing contraction. The arterioles will vasoconstrict. Once again, this pathway need not involve any change in the membrane potential of the smooth muscle cell. Moreover, it does not need to involve changes in cytoplasmic Ca2+ concentration.

β2 adrenergic receptors 1. (like all other adrenergic and muscarinic receptors) work via x. 2. For β receptors, the activated G-proteins stimulate x that catalyzes the conversion of ATP to cAMP, resulting in elevated intracellular cAMP levels. The increased cAMP causes the activation of x. 3. In arteriolar smooth muscle, PKA phosphorylates and inactivates x. Inactivated x cannot phosphorylate myosin of the thick filaments of smooth muscle. You should recall that in smooth muscle only phosphorylated myosin of the thick filaments can bind to actin of the thin filaments and produce contraction. 4. Thus the activation of β2 receptors in arteriolar smooth muscle causes the muscle to x, leading to x. Note that this pathway does not need to involve any change in membrane potential of smooth muscle cells; it is an example of x coupling. 5. Not all arteriolar smooth muscle has β receptors. β2 receptors are primarily found in x smooth muscle of x and the x circulation 6. The role of MLCK (myosin light chain kinase) in smooth muscle explains the seemingly puzzling fact that increased/decreased cytoplasmic cAMP increases/decreases smooth muscle contraction but increases/decreases contraction of the heart. 7. In smooth muscle elevated cAMP leads to x of myosin light chain kinase which INACTIVATES this kinase and thereby reduces the the phosphorylation of myosin, leading to relaxation. 8. In heart, elevated cAMP causes the phosphorylation and activation of x leading to the facilitation of several channel types (as well as the SR Ca2+ pump) with the result of increased/decreased force of contraction.

β2 adrenergic receptors 1. (like all other adrenergic and muscarinic receptors) work via G-proteins. For β receptors, the activated G-proteins simulate adenylyl cyclase that catalyzes the conversion of ATP to cAMP, resulting in elevated intracellular cAMP levels. The increased cAMP causes the activation of protein kinase A (PKA). In arteriolar smooth muscle, PKA phosphorylates and inactivates myosin kinase (myosin light chain kinase). Inactivated myosin kinase cannot phosphorylate myosin of the thick filaments of smooth muscle. You should recall that in smooth muscle only phosphorylated myosin of the thick filaments can bind to actin of the thin filaments and produce contraction. Thus the activation of β2 receptors in arteriolar smooth muscle causes the muscle to relax, leading to vasodilation. Note that this pathway does not need to involve any change in membrane potential of smooth muscle cells; it is an example of pharmacomechanical coupling. Not all arteriolar smooth muscle has β receptors. β2 receptors are primarily found in arteriolar smooth muscle of skeletal muscle and the coronary circulation. The role of MLCK (myosin light chain kinase) in smooth muscle explains the seemingly puzzling fact that increased cytoplasmic cAMP decreases smooth muscle contraction but increases contraction of the heart. In smooth muscle elevated cAMP leads to phosphorylation of myosin light chain kinase which INACTIVATES this kinase and thereby reduces the the phosphorylation of myosin, leading to relaxation. In heart elevated cAMP causes the phosphorylation and activation of PKA leading to the facilitation of several channel types (as well as the SR Ca2+ pump) with the result of increased force of contraction.