Bio 322- Human Anatomy

Bio 322- Human Anatomy • Today’s topics • Muscular system

Organization of muscles and the muscular system • Muscle function: • Movement – • Generate force to move bones – walking, moving body parts • Generate force to move body contents – blood, wastes, food, childbirth, etc… • Stability – • Muscle tone resists force of gravity and helps stabilize some joints • Posture • Communication – • Speaking, writing, facial expressions, etc… • Control of body openings – • SPHINCTER muscles control openings of eyes, mouth, digestive system, urethra, anus • Heat production - • Muscles generate a lot of heat when contracting (85% of body heat) • Keeps body around 98.6 degrees – important for enzyme function! These functions may be carried out by skeletal, smooth, or cardiac muscle, but we’ll mostly focus on skeletal muscle

Connective tissues of a muscle • A muscle (biceps brachii, pectoralis, etc..) is an organ made up of 1,000s of individual muscle cells (MUSCLE FIBERS) that work together to generate force • Multiple layers of connective tissue allows for attachment to bone and is important for organization of the muscle fibers • Keeps muscle fibers organized and packed tightly together • Connective tissue merges with tendons to attach to bone

Connective tissues of a muscle • ENDOMYSIUM : areolar connective tissue that surrounds EACH muscle fiber • Allows blood vessels and nerves access the muscle fiber • Muscle fibers are grouped together in bundles called FASCICLES (maybe 10 fibers per fascicle) • PERIMYSIUM : Thicker connective tissue that surrounds EACH FASCICLE • Fascicles can be seen with the naked eye as “grains” – like on a piece of steak • EPIMYSIUM : Thicker connective tissue that surrounds the ENTIRE MUSCLE • Keeps fascicles bundled together • FASCIA : Connective tissue that surrounds and separates muscles from other tissues • DEEP FASCIA – separates one muscle from another (ex.: between biceps brachii and brachialis) • SUPERFICIAL FASCIA – contains adipose tissue and separates muscles from overlying skin (ex.: between biceps and skin of arm) • Blends into and is hard to differentiate from epimysium Innermost Thinnest Outermost Thickest

Connective tissues of a muscle Attachment of muscle to bones • DIRECT : connective tissue surrounding muscle (epimysium) fuses directly with the periosteum of the bone • INDIRECT : Epimysium and deep facia transitions into a tendon which then inserts into the periosteum of a bone • Very common, creates a physical gap between muscle and bone • APONEUROSIS : Broad, sheet-like tendon that fuses muscle to bone (abdominal muscles) Aponeurosis of external oblique

Muscle anatomy terminology Most muscles of the body are attached to different bones on either end. The contraction of the muscle causes the movement of one of the bones • ORIGIN – the stationary attachment point of a muscle to a bone – this bone does not move when muscle is contracted • INSERTION : the moveable attachment point of a muscle to a bone – this bone moves when the muscle contracts

Actions of groups of muscles • Very often, two or more muscle act together to produce movement at a joint • Ex.: Biceps brachii and brachialis both act to flex the forearm • AGONIST : muscle that produces the most force during a particular movement • SYNERGIST: muscle that aids the agonist in producing a given movement • Usually insertion is different than that of the agonist • ANTAGONIST : muscle that opposes the agonist – creates movement in a joint that is in the opposite direction of the agonist • FIXATOR: a muscle whose function is to prevent movement of ANOTHER bone • Instrinsic muscles have an origin and insertion in the SAME region (tongue, back muscles, etc..) • Extrinsic muscles have an origin and insertion in DIFFERENT regions • Flexor digitorumsuperficialis originates on humerus and proximal radius (elbow and forearm) but inserts on the phalanges

Skeletal muscle histology (more than one, located near plasma membrane) (long and cylindrical) (thin C.T. that surrounds EACH muscle fiber) (due to overlapping of actin and myosin) • Muscle fibers have several nuclei because they come from the fusion of several MYOBLASTS • Occurs during embryonic development • Undifferentiated myoblasts exist in adults as SATELLITE CELLS (a form of stem cell)

Microscopic anatomy of a muscle fiber • Like all cells, muscle cells have a nucleus, plasma membrane, cytoplasm, etc… • In muscle cells some structures have special names: • Plasma membrane = SARCOLEMMA • Cytoplasm = SARCOPLASM • Endoplasmic reticulum = SARCOPLASMIC RETICULUM • - VERY important to muscle fiber function because it acts as the internal storage site of Ca2+ (needed for muscle contraction)

Microscopic anatomy of a muscle fiber • The vast majority of space inside a cell is occupied by the protein filaments that cause the cell to contract – bundles of filaments (called MYOFILAMENTS) combine to form MYOFIBRILS • Larger muscle fibers will contain more myofibrils • Other essential organelles (mitochondria, ER, etc…) are packed in between the myofibrils • The sarcoplasmic reticulum forms a loose network around each myofibril • Dilations of the S.R. are known as TERMINAL CISTERNAE (contain a great deal of Ca2+) NOTE: this image shows ONE muscle cell (fiber) Myofilaments (Thick/thin filaments) Myofibrils Muscle Fiber

Microscopic anatomy of a muscle fiber • TRANSVERSE TUBULES (T-tubules) small tubes that are created by the infolding of the sarcolemma • The T-tubule combines with two terminal cisternae on either side to form a TRIAD • The T-tubule carries electrical signals (nerve impulses) to the inside of the cell and triggers the release of Ca2+ from the SR and terminal cisternae Nerve impulse

Molecular structure of myofibrils • Each MYOFIBRIL consists of a bundle of long, parallel myofilaments : Thick filaments, thin filaments, elastic filaments • Thick Filaments – • Made up of hundreds of protein molecules called MYOSIN – shaped like a golf club • Myosin molecules are arranged end-to-end in a spiral fashion with the “heads” facing outward • Thin filaments – • Made up of long winding strands of the protein ACTIN • Actin molecule has an ACTIVE SITE to bind to the myosin head • When a muscle is relaxed, the active sites of actin are covered up by two proteins called TROPOMYOSIN and TROPONIN – myosin can’t bind to actin and cause contraction • Elastic filaments – • Smallest of the filaments – made up of protein called TITIN • A stretchy filament that anchors the thick filaments in place

Molecular structure of myofibrils • Myosin and actin are considered CONTRACTILE PROTEINS since they are responsible for the actual shortening of the muscle fiber (contraction) • Tropomyosin and troponin are considered REGULATORY PROTEINS since their job is to regulate when and if a muscle cell will contract • There are also a number of accessory proteins that also play a role in muscle fiber contraction • DYSTROPHIN – a HUGE protein that anchors actin filaments to the endomysium • Links the shortening muscle fiber to external CT • This protein is mutated and non-functional in the disease MUSCULAR DYSTROPHY

Organization and association of sarcomere elements with linking proteins, sarcolemma, and endomysium • Linking proteins such as dystrophin allows muscle cell to translate shortening of sarcomere into shortening of muscle cell and shortening of muscle tissue

Organization of filaments in a myofibril • The thick, thin, and elastic filaments are arranged in a VERY specific, ordered fashion that allows contraction to occur efficiently • Z-DISK is a large protein that the thin filaments and elastic filaments are attached to • Z-disk is also attached to sarcolemma – helps translate contraction of myofibrils to contraction of muscle fiber • Thick filaments are suspended between the thin filaments by elastic filaments • Two Z-disks with the associated thick and thin filaments in between is called a SARCOMERE – the functional unit of contraction in a myofibril • Contraction brings the Z-disks closer together, shortening the length of the sarcomere = CONTRACTION!!

Organization of filaments in a myofibril • Remember that skeletal muscle contains STRIATIONS – alternating bands of light and dark • The I-band (light band) of the sarcomere contains only elastic filaments and thin filaments • The A-band (dark band) contains overlapping thin, thick, and elastic filaments • LIGHT = I -band DARK = A-band • The H-band is the region in the middle where there are only thick filaments since the thin filaments do not extend that far – only present in RELAXED sarcomere

Role of the nervous system in muscle contraction • Specialized neurons that trigger muscle contraction are known as MOTOR NEURONS • As the axon of a motor neuron approaches the muscle it branches out into dozens of smaller fibers – allows one nerve to stimulate MANY different muscle fibers • This arrangement helps coordinate the timing of the contractions of the 1000s of muscle fibers found in a muscle • Although each nerve fiber can stimulate 100s of muscle fibers, one muscle fiber can only be stimulated by ONE nerve fiber – prevents the muscle fiber from getting “mixed signals”

Role of the nervous system in muscle contraction • When a motor neuron sends an impulse, ALL of the muscle fibers associated with it contract at the same time – this group of muscle fibers is called a MOTOR UNIT • Large muscles may have 100s of different motor units • Strength of muscle contraction depends on number of motor units stimulated • The muscle fibers of a motor unit are often spread out over a fairly large area • The process of adding more motor units during a strong contraction = RECRUITMENT • Ability to vary # of motor units (i.e., strength of contraction) allows for fine control of small movements

Role of the nervous system in muscle contraction • Having many motor units is important for repeated or sustained muscle contractions • Eventually, some motor units get tired and others will take over (like shift work) • Not all motor units contain the same # of muscle fibers • Activation of smaller motor units allow for weaker muscle contractions (better suited for fine movements) • Activation of larger motor units lead to strong contractions (better suited for gross movements) • Weak nerve impulse = fewer and smaller motor units • Stronger impulses = more, larger motor units

The neuromuscular junction How does a nerve “tell” a muscle when and how to contract??? • Neurons “talk” to muscle fibers via the NUEROMUSCULAR JUNCTION • Interaction between a motor neuron and a muscle fiber is a SYNAPSE • Nerves don’t physically contact muscle fibers – separated by a very small gap called the SYNAPTIC CLEFT • Motor neurons communicate with muscle cells using the neurotransmitter ACETYLCHOLINE (ACh)

The neuromuscular junction • Motor nerves contain an large bulb at their ends called a SYNAPTIC BULB • This bulb contains vesicles filled with ACh • The sarcolemma of the muscle fiber contains 100s of ACh receptors near the neuromuscular junction • Arrival of a nerve impulse at the synaptic bulb trigger the exocytosis of ACh • ACh travels across the synaptic cleft and binds to ACh receptors on the sarcolemma • The binding of ACh to receptors on the muscle fiber initiates events that cause contraction • After the ACh binds to receptors on the muscle fiber it is rapidly degraded by ACETYLCHOLINESTERASE

Excitation of cells of the muscular system • Motor neurons and muscle fibers are both known as ELECTRICALLY EXCITABLE • The voltage across the cell membrane changes when the cell is stimulated • When there is a charge difference across the cell membrane, the cell is said to be POLARIZED • Negative = iNside , pOsitive = Outside • Lots of Na+ outside; DNA, proteins, other anions inside Na+ Na+ Na+ _ _ DNA, protein, phosphate K+ _ _ Na+ K+ K+ _ _ Na+ _ Na+ Na+ • The electrochemical Na+ gradient (more outside) is maintained by the Na+/K+ ATPase– pushes Na+ outside against its conc. gradient

Excitation of cells of the muscular system • Stimulation of nerve or muscle cell leads to DEPOLARIZATION of the cell membrane • Stimulus causes Na+ ion channels to open • Na+ rushes in (down conc. gradient) • For a BRIEF period the inside of the cell becomes positively charged • Depolarization causes Na+ channels to close and K+ channels to open • K+ rushes out (down its conc. gradient) • Loss of (+) charged K+ allows inside of cell to regain negative charge • Return of membrane charge (− inside, + outside) is called REPOLARIZATION • The change of the cell interior from (–) to (+) and then back to (-) is known as an ACTION POTENTIAL Na+ Na+ Na+ Na+ Na+ Na+ _ _ _ _ DNA, protein, phosphate DNA, protein, phosphate K+ K+ _ _ _ _ Na+ Na+ K+ K+ K+ K+ _ _ _ _ Na+ Na+ Na+ Na+ Na+ Na+ DEPOLARIZED _ _ _ _ Na+ Na+ DNA, protein, phosphate K+ Na+ _ Na+ POLARIZED Na+ K+ K+ REPOLARIZED Na+ Na+ _ _

Localization of an action potential • When the membrane of a nerve or muscle cell experiences an ACTION POTENTIAL (polarization, depolarization, repolarization), this is a LOCAL occurrence • Only a small part of the muscle cell membrane is depolarized at a given time • Think of “The Wave” at a sports event DEPOLARIZATION NERVE OR MUSCLE FIBER DEPOLARIZATION NERVE OR MUSCLE FIBER DEPOLARIZATION REPOLARIZATION NERVE OR MUSCLE FIBER • Depolarization of a region is IMMEDIATELY followed by repolarization • Necessary to allow a nerve or muscle cell to be restimulated • Depolarization of one region triggers the depolarization of a region next to it • Allows action potentials to be self-propagating REPOLARIZATION

Excitation of skeletal muscle Motor end plate • Nerve impulse arrives at synaptic bulb • Entrance of Ca2+ into synaptic bulb triggers exocytosis of ACh-containing vesicles • ACh travels across synaptic cleft and binds to ACh receptors on sarcolemma • The region of the muscle fiber where ACh binds is called the MOTOR END PLATE-the muscle part of the neuromuscular junction

Excitation of skeletal muscle • The ACh receptors actually play two roles : ACh receptor AND ion channel • LIGAND-GATED ION CHANNEL – opens up when ACh binds • Binding of ACh (ligand) to its receptor causes conformational change that “opens” up the ion channel • Na+ ions rush IN, causing voltage across membrane to reverse (depolarize) • Slower diffusion of K+ OUT of the cell begins repolarization • This LOCAL fluctuation of membrane voltage (at the motor end plate) leads to the activation of VOLTAGE-GATED ion channels on the REST of the muscle fiber

Location and function of Ligand-gated -vs- Voltage gated ion channels Motor end plate The rest of the muscle cell Na+ Na+ OUTSIDE (+) Ligand Ligand INSIDE (-) Na+ Na+ • Ligand gated ion channels are ion channels that require a ligand in order for them to open and cause depolarization • These channels will only be found at the motor end plate of a muscle cell • When ACh binds to the channel it opens up letting Na+ enter the cell • Voltage gated ion channels are ion channels that require a change in membrane voltage to open and cause depolarization • These channels sense changes in membrane voltage (a nearby depolarization) that triggers them to open up and let Na+ enter the cell • Found over the rest of the muscle cell (but not at motor end plate) • These channels are responsible for propagating the action potential over the surface of a muscle cell

Excitation/Contraction coupling This is the process by which we translate the action potential on the sarcolemma to the contraction of myofilaments inside the muscle cell • Action potentials that leave the motor end plate spread out over the entire surface of the sarcolemma and travel down T-tubules – dependent on voltage gated ion channels • This triggers the opening of voltage-gated Ca2+ channels in the SR • Ca2+ diffuses into sarcoplasm

Excitation/Contraction coupling • Ca2+ released from the SR binds to troponin on the thin filaments and causes troponin to change shape • The troponin/tropomyosin complex shifts position thereby exposing the active sites of the actin molecules • The exposure of the active sites on actin (thin filaments) makes them available to bind to the heads of the myosin molecules (thick filaments)

Contraction • The enzyme MYOSIN ATPase hydrolyzes ATP, releasing energy (ATP→ADP+P +ENERGY) • This energy is used to activate the myosin head • The myosin head “reaches” out to bind to the active site of actin • In the 2nd step, the myosin head binds to the exposed active site of actin, creating a CROSS-BRIDGE

Contraction • After binding to actin, the myosin head releases the ADP+ P causing it to return to its original conformation • This pulls on the actin, causing the thin filament to slide past the thick filament – this brings the Z-disks closer together • Binding of a new molecule of ATP causes the myosin head to release the actin molecule • Hydrolysis of ATP then allows the myosin head to “reach” out to another actin molecule farther down the thin filament • This process repeats over and over until the sarcomere is shortened by about 40% • Each “ratcheting” of the myosin head uses one ATP • Each myosin head ratchets 5X per second • 1000s of myosin heads work together to shorten each muscle fiber – Contraction uses a HUGE amount of ATP!!!

Relaxation • Once the contraction is finished, the motor neuron stops releasing ACh • Remaining ACh bound to the receptors is degraded by ACETYLCHOLINESTERASE • This prevents action potentials from being generated at the motor end plate • Without stimulation, Ca2+ is pumped back INTO the SR – active transport (uses ATP) • As Ca2+ diffuses away from troponin, the tropomyosin molecules cover up the active sites of actin again – prevents myosin from binding • Without myosin binding, the thin filaments slide BACK over the thick filaments and the sarcomere lengthens (returns to resting length)

Summary Arrival of action potential at synaptic bulb of motor neuron causes release of ACh across synaptic cleft (process requires Ca2+) Binding of ACh to sarcolemma at motor endplate creates local action potential (dependent on the availability of ACh from motor neuron) Action potential at motor end plate spreads out over sarcolemma and down T-tubule to SR (these action potentials are generated by voltage gated ion channels and are dependent on the initial ACh-dependent action potential) Release of Ca2+ from SR allows active sites of actin to be bound by myosin heads “Ratcheting” of the myosin heads is dependent on the energy released from ATP hydrolysis “Ratcheting” of myosin causes thin filaments to slide over the thick filaments – brings Z-disks closer to each other (sarcomere shortening) End of motor neuron stimulation causes Ca2+ to be pumped back into SR (diffuses away from troponin) – active transport of Ca2+ requires ATP Myosin releases actin and allows thin filaments to slide back over thick filaments and return to resting position (sarcomere lengthens) Be sure to understand and remember which steps in the entire process require ATP, ACh, or Ca2+ !!!!!!

Bio 322 – Human Anatomy • Today’s topics • Muscular system

Action potential and muscle physiology animations Action potential at Neuromuscular junction Action potentials and muscle contraction Crossbridge formation and contraction contraction of the sarcomere

What factors are needed and when??? Ca2+ ACh ATP • ACh release: • Ca2+ triggers exocytosis of ACh from synaptic bulb • Crossbridge formation: • Ca2+ binds to troponin causing tropomyosin to shift positions and expose active sites of actin • Maintenance of cell polarization: • Na+/K+ ATPase requires ATP to maintain Na+ gradient thereby keeping interior of cell negatively charged • Muscle fiber contraction: • Myosin heads use ATP to “reach” out and attach to active sites of actin • Muscle fiber relaxation: • Ca2+ pumps use active transport to pump Ca2+ BACK into the SR • Action potential generation: • ACh binds to receptors on sarcolemma of motor end plate causing Na+ channels to open and lead to depolarization of sarcolemma • Without this initial action potential there can be NO MUSCLE CONTRACTION

Length-Tension relationship and muscle tone • The amount of force or tension a muscle can generate is related to how contracted or stretched it was prior to stimulation • Remember that muscle contraction is dependent on the overlapping of thick and thin filaments • If a muscle is overly stretched or contracted before stimulation → weak contraction • A -OPTIMAL RESTING LENGTH the thin filaments are just overlapping with all the myosin heads → maximal contraction • B – When the muscle is overly contracted the thin filaments overlap the thick filaments so much that the thick filaments are nearly butting up against the Z-disk → no room for additional sarcomere shortening • C – When the muscle is overly stretched only a SMALL part of the thin filament overlaps with the thick filaments → myosin heads on thick filaments can’t “get a hold” of thin filaments A B C

Muscle tone • Even at rest, muscles maintain a certain degree of contraction called MUSCLE TONE • This allows the sarcomeres of the muscle fibers to remain at their optimal length • Helps ensure that the muscle is ready for maximal contraction at all times • Muscle tone is important for posture, balance, and joint stability • Muscles of the trunk and legs keep us centered and upright WITHOUT conscious effort • Muscle tone in deltoid and biceps brachii helps stabilize shoulder joint • Stretch receptors within muscle tissue is known as MUSCLE SPINDLE Muscle Spindle Motor neuron

Different types of muscle contractions • Not every muscle contraction results in shortening of the muscle length and movement of a body part • Muscle contraction technically refers to the generation of force and tension within a muscle • Isometric contraction (constant length) – muscle contracts (develops tension in elastic components of muscle tissue) but DOES NOT SHORTEN in length • Isotonic contraction (constant force) – muscle contracts (develops tension) and may either lengthen or shorten depending on force of contraction – think of trying to lift a 5lb bar versus a 500lb bar • Both of these contractions are in play when we lift a weight

Isometric and Isotonic contractions • Example : Lifting a 50lb weight off of the floor • Requires both isometric and isotonic contraction • After you grab the weight, you increase muscle contraction (tension) but have not yet moved the weight from the floor • Tension increases, but muscle length stays the same (ISOMETRIC CONTRACTION) • Eventually you generate enough force (tension) to overcome gravity and you lift the weight off the floor • Tension stays the same but the muscle shortens as you move the weight (ISOTONIC CONTRACTION) At this point muscle tension exceeds the load and the muscle is allowed to shorten

Classes of muscle fibers • Skeletal muscle fibers can be divided into 2 main categories – SLOW TWITCH (oxidative) and FAST TWITCH (glycolytic) • Slow and fast twitch fibers differ in function and metabolic needs, and are more suited for certain functions • Nearly all muscles contain a mixture of slow and fast twitch fibers - difference is in proportion • All of the muscle fibers from a given motor unit contain ONLY fast or slow twitch – not mixed Slow Twitch muscle fibers • These fibers exhibit a slower twitch (longer cycle of contraction/relaxation) – about 100 msec/twitch • They possess lots of mitochondria (site of ATP generation), myoglobin (O2 stores in muscle), and are well supplied with blood vessels • Well-suited to aerobic respiration • Very resistant to physiological fatigue • Muscles with lots of slow twitch fibers have a dark red appearance – “red meat” • Since these fibers do not fatigue easily, they are found in higher abundance in muscles requiring long, sustained contractions – calf muscles (walking), back and trunk muscles (posture)

Fast twitch muscle fibers • These fibers twitch more rapidly – about 7.5 sec/twitch • These fibers contain less mitochondria, less myoglobin, and fewer blood vessels, BUT MORE components required for anaerobic fermentation and phosphagen system (myokinase/creatinekinase) – needed for immediate and short term energy • More susceptible to physiological fatigue • Have a lighter appearance than slow twitch – “white meat” • Sarcoplasmic reticulum is more able to quickly release/absorb Ca2+ - more rapid and forceful contractions • Since they rely on anaerobic fermentation, they produce a lot of lactic acid – causes fatigue • Ability to produce short, forceful contractions makes them suited for larger, less used (relatively) muscles – arm, leg muscles

Slow twitch Fast twitch White meat –vs.- dark meat What can you tell about the different muscles of a chicken???

Cardiac Muscle • Striated like skeletal muscle (overlapping thick and thin filaments) • Intercalated disks and mechanical junctions allow one cardiac muscle cell to stimulate its neighbors and remain tightly connected – unlike skeletal muscle • Cardiomyocytesdon’t necessarily need nervous system input (at least not the way skeletal muscles do) • Stimulation of specialized cells trigger contraction of muscle cells throughout the heart (via intercalated disks) • Twitches are very slow compared to skeletal muscle (about 250 msec) – allows the heart to contract and expel all the blood it contains • Relies almost exclusively on aerobic respiration – very resistant to fatigue (GOOD!) • Lots of myoglobin, mitochondria, glycogen stores (around nucleus) • This also makes cardiac muscle VERY susceptible to damage from disruptions of blood flow

Smooth muscle • Tapered cells with NO STRIATIONS • Cells DO contain thick and thin filaments, but not arranged in away so that the cell appears striated • Thick and thin filaments attach to plasma membrane via a complex internal cytoskeleton and protein masses called DENSE BODIES • Thin filaments attach to dense bodies and cytoskeleton instead of Z-disks (skeletal muscle) • Need Ca2+ for contraction, like all muscle • Ca2+ comes primarily from extracellular fluid, NOT FROM SARCOPLASMIC RETICULUM • Ca2+ flows into cell via channels (contraction) • Ca2+ is pumped out during relaxation

Stimulation, contraction, relaxation of smooth muscle • Like cardiac muscle, smooth muscle is involuntary and doesn’t necessarily need nerve stimulation to contract (but often does) • Can also contract in response to hormones, CO2 levels, changes in pH, stretch, etc… • Ca2+ channels are opened in response to these factors • This is how some smooth muscle contraction is regulated in the stomach, intestines, blood vessels, etc… • There are 2 main types of smooth muscle: • Multiunit smooth muscle – requires innervation from autonomic nervous system (involuntary). Nerve fibers innervate many smooth muscle cells creating a motor unit (like skeletal muscle) • Single unit smooth muscle – muscle cells communicate via gap junctions. Nerve fiber releases ACh near one cell and the stimulation is passed to other connected cells (like cardiac cells)

Stimulation, contraction, relaxation of smooth muscle • Although smooth muscle contains thick and thin filaments and requires Ca2+ for contraction, it contains no troponin as a regulatory protein • Smooth muscle contains a unique protein called calmodulin • Associated with THICK FILAMENTS • When calmodulin binds Ca2+ it activates an enzyme that transfers phosphate group from ATP to myosin head (PHOSPHORYLATION=adding phosphate to a protein). • Myosin then binds to actin and uses ANOTHER ATP to “ratchet” • Process uses 2 ATP molecules as opposed to skeletal muscle (only 1 ATP) • Regulation occurs at thick filament, not at thin filament like skeletal muscle • When thick filaments “ratchet” they pull on thin filaments that are attached to DENSE BODIES and cytoskeleton → contraction of the muscle cell

Stimulation, contraction, relaxation of smooth muscle • As compared to skeletal muscle, smooth muscle twitch is VERY SLOWLY • Pumping Ca2+ into/out of the cell occurs much more slowly without a SR (like skeletal muscle) • “Ratcheting” of smooth muscle myosin requires more steps and uses more ATP • Phosphorylation/dephosphorylation of myosin is slow • For smooth muscle to relax 2 things need to occur: • Removal of Ca2+ - inactivates calmodulin • Dephosphorylation of myosin • However, in some cases, smooth muscle can stay contracted even in the absence of ATP – allows some muscles to remain contracted without using ATP

Bio 322- Human Anatomy