Lec 11 - Smooth Muscle, Cardiac Muscle, Overview of the Cardiovascular System

How is smooth muscle classified by location?

Vascular, gastrointestinal, urinary, respiratory, reproductive, ocular

How is smooth muscle classified by contraction pattern?

Phasic smooth muscles and tonic smooth muscles

Examples of tonic smooth muscle?

Esophageal and urinary bladder sphincters

How is smooth muscle classified by communication with neighboring cells?

Single-unit (unitary, visceral) smooth muscle and multiunit smooth muscle

Fig 12.23a: Single-unit smooth muscle?

Cells are connected by gap junctions and contract as a single unit (e.g., small intestine; autonomic neuron varicosity releases neurotransmitter)

Fig 12.23b: Multiunit smooth muscle?

Cells are not electrically linked; each cell must be stimulated independently (e.g., eye; neuron varicosities)

Fig 12.24: Which muscle type is slowest to contract and relax?

Smooth muscle (twitch lasts about 5 sec); skeletal is fastest, cardiac is intermediate

Smooth muscle: sarcomeres?

Lacks sarcomeres

Smooth muscle actin?

More plentiful (10-15 actin : 1 myosin); associated with tropomyosin but smooth muscle lacks troponin

Smooth muscle myosin?

Filaments are longer; entire surface of filament covered with myosin heads

Smooth muscle cytoskeleton?

Extensive: intermediate filaments and dense bodies

Smooth muscle sarcoplasmic reticulum?

Amount varies and is less organized; no t-tubules but caveolae

Fig 12.25a: Smooth muscle organization?

Intermediate filaments and protein dense bodies form a cytoskeleton; actin attaches to dense bodies; each myosin molecule is surrounded by actin filaments; connective tissue links cells

Fig 12.25b: Smooth muscle myosin?

Has hinged heads all along its length

What initiates smooth muscle contraction?

Increase in cytosolic Ca2+ (from SR and ECF via caveolae)

Where does Ca2+ bind in smooth muscle?

Calmodulin

Smooth muscle cascade?

Ca2+ binds calmodulin > calmodulin activates myosin light chain kinase (MLCK) > MLCK phosphorylates myosin light chains (MLC) > enhances myosin ATPase activity

What causes dephosphorylation of MLC?

Myosin light chain phosphorylase (MLCP)

Latch state?

Dephosphorylated myosin may remain attached to actin for a period of time

What does MLCP control?

Ca2+ sensitivity

Smooth muscle vs skeletal/cardiac mechanism?

No troponin complex; calmodulin shuttles calcium in the cell; mechanism of contraction differs, but myosin-actin interaction is the same

Electromechanical coupling?

Contraction caused by electrical signaling

Pharmacomechanical coupling?

Contraction caused by chemical signaling

Sarcoplasmic Ca2+ release channels/mechanisms in smooth muscle?

Ryanodine receptor (RyR) calcium release channel; IP3-receptor channel; calcium-induced calcium release (CICR); store-operated Ca2+ channels

Fig 12.26: How does smooth muscle differ from skeletal?

(1) Ca2+ comes from ECF as well as SR; (2) action potential not required for Ca2+ release; (3) no troponin, so Ca2+ acts through a cascade that phosphorylates myosin light chains; (4) relaxation needs dephosphorylation of myosin light chains by myosin phosphatase

Fig 12.26a: Contraction steps?

1) Intracellular Ca2+ rises (entry and SR release). 2) Ca2+ binds calmodulin (CaM). 3) Ca2+-CaM activates MLCK. 4) MLCK phosphorylates light chains on myosin heads, increasing myosin ATPase activity. 5) Active myosin crossbridges slide along actin and create tension

Fig 12.26b: Relaxation steps?

6) Free cytosolic Ca2+ falls as it is pumped out of the cell or back into the SR. 7) Ca2+ unbinds from CaM; MLCK activity decreases. 8) Myosin phosphatase (MLCP) removes phosphate from myosin light chains, decreasing ATPase activity. 9) Less ATPase activity = decreased tension

Fig 12.26b: First step in relaxation?

Removal of Ca2+ from the cytosol

Fig 12.27: How does phosphatase activity alter Ca2+ response?

Low phosphatase activity sensitizes myosin (curve shifts left); high phosphatase activity desensitizes myosin (curve shifts right); y-axis is myosin light chain phosphorylation and force vs [Ca2+]

Three ways Ca2+ enters across the cell membrane?

1) Voltage-gated Ca2+ channels. 2) Ligand-gated (receptor-operated, ROCC) Ca2+ channels. 3) Stretch-activated Ca2+ channels

Stretch-activated calcium channels?

Open when pressure or other force distorts the cell membrane; myogenic contraction

Unstable membrane potentials in smooth muscle?

Slow-wave potentials and pacemaker potentials

Fig 12.28a: Slow wave potentials?

Fire action potentials when they reach threshold

Fig 12.28b: Pacemaker potentials?

Always depolarize to threshold; associated with interstitial cells of Cajal (ICC)

Fig 12.29: Stimuli and routes to smooth muscle contraction?

Signal ligands (norepinephrine, ACh, other neurotransmitters, hormones, paracrine signals) act on membrane receptors; depolarization or stretch acts on membrane channels; store-operated Ca2+ channels open when SR Ca2+ stores decrease

Fig 12.29: Pathways in the cell?

Membrane receptors > increased IP3 > IP3-R on SR > Ca2+ release; membrane channels > increased Ca2+ entry; modulatory pathways alter MLCK or myosin phosphatase; all lead to muscle contraction (IP3-R = IP3-activated receptor channel)

Table 12.4: Appearance?

Skeletal striated; smooth smooth; cardiac striated

Table 12.4: Fiber arrangement?

Skeletal sarcomeres; smooth no sarcomeres; cardiac sarcomeres

Table 12.4: Location?

Skeletal: attached to bones (a few sphincters). Smooth: walls of hollow organs and tubes; some sphincters. Cardiac: heart

Table 12.4: Tissue morphology?

Skeletal: multinucleate, large cylindrical fibers. Smooth: uninucleate, small spindle-shaped fibers. Cardiac: uninucleate, shorter branching fibers

Table 12.4: Internal structure?

Skeletal: T-tubule and SR. Smooth: no t-tubules; SR. Cardiac: T-tubule and SR

Table 12.4: Fiber proteins?

Skeletal: actin, myosin, troponin, tropomyosin. Smooth: actin, myosin, tropomyosin. Cardiac: actin, myosin, troponin, tropomyosin

Table 12.4: Control?

Skeletal: Ca2+ and troponin; fibers independent; Ca2+ from SR. Smooth: Ca2+ and calmodulin; some fibers linked via gap junctions, others independent; Ca2+ from ECF and SR. Cardiac: Ca2+ and troponin; fibers linked via gap junctions; Ca2+ from ECF and SR

Table 12.4: Contraction speed?

Skeletal fastest; smooth slowest; cardiac intermediate

Table 12.4: Force of single fiber twitch?

Skeletal not graded; smooth graded; cardiac graded

Table 12.4: Initiation of contraction?

Skeletal: requires ACh from motor neuron. Smooth: stretch, chemical signals; can be autorhythmic. Cardiac: autorhythmic

Table 12.4: Neural control?

Skeletal: somatic motor neuron. Smooth: autonomic neurons. Cardiac: autonomic neurons

Table 12.4: Hormonal influence?

Skeletal: none. Smooth: multiple hormones. Cardiac: epinephrine

Cardiac muscle: like skeletal muscle?

Striated; sarcomere structure

Cardiac muscle: unlike skeletal muscle?

Fibers are shorter, may be branched, have a single nucleus

Cardiac muscle: like smooth muscle?

Electrically linked to one another; some exhibit pacemaker potentials; under sympathetic, parasympathetic and hormone control

Cardiac muscle: unlike smooth muscle?

Gap junctions in intercalated disks

Intercalated disc: components?

Desmosomes (link plasma membranes of adjacent cardiac fibers) and gap junctions (pass action potentials)

Cardiac EC coupling steps?

Action potential in contractile cell > travels down T tubules > small Ca2+ entry from ECF via L-type Ca2+ channels > Ca2+-induced Ca2+ release of large Ca2+ amount from SR via ryanodine receptor channels > cytosolic Ca2+ rises > troponin-tropomyosin pulled aside > crossbridge cycling > thin filaments slide inward > contraction

L-type Ca2+ channels = ?

Dihydropyridine receptors (DHPRs)

Ryanodine receptor (RyR)?

Calcium-release channel of the sarcoplasmic reticulum (SR)

Components of the cardiovascular system?

Heart, blood vessels (vasculature), and blood

Blood vessels?

Arteries vs veins; capillaries; a portal system joins two capillary beds in series

Heart: septum, atrium, ventricle?

Septum divides heart into left and right halves; atrium receives blood returning to the heart; ventricle pumps blood out of the heart

Blood is made of?

Cells and plasma

Pulmonary vs systemic circulation?

Pulmonary arteries vs pulmonary veins; aorta vs inferior vena cava and superior vena cava

Fig 14.1: Circulation parts labeled?

Veins, capillaries, arteries; head and brain, arms, lungs, trunk, liver, digestive tract, kidneys, pelvis and legs

Fig 14.1: Heart and great vessels labeled?

Right/left atrium, right/left ventricle, aorta, superior/inferior vena cava, pulmonary arteries and veins, coronary arteries

Fig 14.1: Liver and kidney vessels?

Hepatic artery, hepatic portal vein, hepatic vein; renal arteries, renal veins

Fig 14.1: Other vessels labeled?

Ascending arteries, abdominal aorta, descending arteries, ascending veins, venous valve

Learning outcomes for this lecture?

Diagram smooth muscle anatomy; diagram smooth muscle contraction and relaxation; explain slow wave potentials, pacemaker potentials and pharmacomechanical coupling; compare and contrast cardiac muscle with skeletal and smooth muscle

Key words?

phasic smooth muscles, tonic smooth muscles, sphincters, single-unit smooth muscle (unitary or visceral), multiunit smooth muscle, dense bodies, calmodulin, myosin light chain kinase (MLCK), myosin light chain, myosin light chain phosphatase (MLCP), slow wave potentials, pacemaker potentials, arteries, veins