Muscle Physiology Lecture Notes

Skeletal Muscle

• Structure
  • Striated muscle due to alternating light and dark bands perpendicular to the long axis.
  • Muscle fiber: Elongated, multinucleated cell formed by fusion of myoblasts.
  • Satellite cells: Undifferentiated stem cells that repair damaged muscle fibers; can also cause hypertrophy (increase in size) of remaining muscle fibers.
  • Muscle: Bundle of skeletal muscle fibers bound together by connective tissue.
  • Tendons: Connective tissue (collagen fibers) attaching muscles to bones.

Filament Structure

• Thick Filaments

  • Composed of myosin.
  • Myosin molecule: Two heavy chains and four light chains, forming globular heads and a long tail.
  • Cross-bridges: Globular heads extending from thick filaments, contacting thin filaments and exerting force.
  • Myosin-ATPase: Enzyme in globular heads that hydrolyzes ATP for contraction.

• Thin Filaments

  • Composed of actin, nebulin, troponin, and tropomyosin.
  • Actin: Globular protein monomers polymerizing into intertwined helical chains; contains myosin-binding sites.
  • Tropomyosin and Troponin: Regulatory proteins. When a muscle is relaxed Tropomyosin lies on top of the myosin binding site on each actin monomer, thereby preventing the heads from making contact with actin. One molecule of troponin binds to each molecule of tropomyosin, regulating access to myosin-binding sites on the seven actin monomers in contact with that tropomyosin.

• Sarcomere Structure

  • Sarcomere: Repeating unit of thick and thin filaments between two Z lines.
  • A band: Wide, dark band in the middle of the sarcomere, containing thick filaments.
  • I band: Light band between A bands of adjacent sarcomeres, containing thin filaments not overlapping thick filaments; bisected by the Z line.
  • Z line: Network of proteins where thin filaments anchor.
  • H zone: Narrow, light band in the center of the A band corresponding to the space between the opposing ends of the two sets of thin filaments in each sarcomere.
  • M line: Dark band in the center of the H zone, linking central regions of adjacent thick filaments.
  • Titin: Elastic protein filaments extending from the Z line to the M line that maintain alignment of thick filaments, contributing to muscle's passive elastic properties.

  Other Myofibril Structures

• Sarcoplasmic Reticulum

  • Sleevelike segments around myofibrils; homologous to endoplasmic reticulum.
  • Terminal cisternae (lateral sacs): Enlarged regions at the end of each segment.
  • Calsequestrin: Ca2+-binding protein in terminal cisternae, storing Ca2+.

• Transverse Tubules (T-tubules)

  • Lie between terminal cisternae of adjacent sarcoplasmic reticulum segments.
  • Continuous with the plasma membrane (sarcolemma), propagating action potentials.
  • Lumen is continuous with extracellular fluid.

• Review

  • Skeletal muscles: Cylindrical, multinucleated muscle fibers (cells) derived from myoblasts linked to bones by tendons at each end of a muscle
  • Satellite cells: Undifferentiated stem cells that proliferate and differentiate into myoblasts in response to damage of a muscle
  • Hypertrophy: An increase in size of muscle fibers that may occur in response to injury or to exercise
  • Sarcomeres: Repeating, striated pattern of light and dark bands observed when viewing skeletal muscle fibers under a microscope
  • Striated pattern is due to arrangement of thick and thin filaments arranged in bundles (myofibrils); form A and I bands; Z and M lines, and H zone.
  • Thin filaments: Contain actin, troponin, and tropomysin; anchored to the Z lines at each end of a sarcomere; free ends partially overlap the myosin-containing thick filaments in the A band at the center of the sarcomere
  • Thick filament: Made up of myosin molecules with extensions called cross-bridges that span the gap between the thick and thin filaments
  • Each cross-bridge has two globular heads that contain a binding site for actin and an enzymatic site (myosin- ATPase) that hydrolyzes ATP.
  • Electrical activation of skeletal muscle fibers: Transmitted via elaborations of the plasma membrane (sarcolemma)
  • called transverse tubules (T-tubules)
  • T-tubules interact with terminal cisternae of the sarcoplasmic reticulum, to release stored Ca2+ into the cytosol.

Molecular Mechanisms of Skeletal Muscle Contraction

• Contraction: Activation of force-generating sites (cross-bridges) within muscle fibers; does not necessarily mean shortening.

• Relaxation: Force-generating mechanisms are turned off, and tension declines.

• Membrane Excitation: The Neuromuscular Junction

  • Alpha motor neurons: Neurons innervating skeletal muscle fibers; cell bodies in brainstem and spinal cord.
  • Motor unit: A motor neuron and all the muscle fibers it innervates.
  • Neuromuscular junction: Synapse between a motor neuron axon terminal and the motor end plate of a muscle fiber.
  • Motor end plate: Region of muscle fiber plasma membrane under the axon terminal, containing acetylcholine (ACh) receptors.
  • Junctional folds: increase the surface area of the motor end plate.
  • Action potential arrives at the axon terminal, depolarizing the plasma membrane.
  • Voltage-sensitive Ca^{2+} channels open, allowing calcium ions to diffuse into the axon terminal from the extracellular fluid.
  • Ca^{2+} binds to proteins that enable the membranes of ACh-containing vesicles to fuse with the neuronal plasma membrane, releasing ACh into the synaptic cleft.
  • ACh diffuses to the motor end plate, where it binds to ionotropic receptors of the nicotinic type.
  • The binding of ACh opens an ion channel in each receptor protein; allowing more Na^{+} moves in than K^{+} out, producing a local depolarization of the motor end plate known as an end-plate potential (EPP).
  • End-plate potential (EPP): Depolarization of the motor end plate due to opening of ACh-gated ion channels; analogous to an EPSP.
  • Acetylcholinesterase: Enzyme in the synaptic cleft that breaks down ACh.

• Disruption of Neuromuscular Signaling

  • Curare: Binds to nicotinic ACh receptors, blocking ACh binding and causing paralysis.
  • Organophosphates: Inhibit acetylcholinesterase, causing ACh buildup and depolarization block.
  • Botulinum toxin: Blocks ACh release from axon terminals.

• Excitation–Contraction Coupling

  • Sequence of events by which an action potential activates force-generating mechanisms.
  • Action potential in plasma membrane increases cytosolic Ca^{2+} concentration.
  • Tropomyosin: Rod-shaped molecule that blocks myosin-binding sites on actin.
  • Troponin: Globular protein that binds to tropomyosin and actin; contains three subunits: I (inhibitory), T (tropomyosin-binding), and C (Ca2+-binding).
  • Calcium binds to Troponin, relaxing its inhibitory grip and allowing Tropomyosin to move away from the myosin-binding site on each actin molecule. Conversely, the removal of calcium from troponin reverses the process, turning off contractile activity.

• Mechanism of Cytosolic Increase in Ca^{2+}

  • T-tubules are in contact with the terminal cisternae of the sarcoplasmic reticulum, connected by structures known as junctional feet, or foot processes.
  • Dihydropyridine (DHP) receptor: Voltage-sensitive Ca2+ channel in T-tubule membrane; acts as a voltage sensor.
  • Ryanodine receptor: Protein in sarcoplasmic reticulum membrane that forms a Ca^{2+} channel.
  • During a T-tubule action potential, charged amino acid residues within the DHP receptor protein induce a conformational change, which acts via the foot process to open the ryanodine receptor channel.

• Sliding-Filament Mechanism

  • Thick and thin filaments slide past each other, propelled by cross-bridge movements.
  • Sarcomeres shorten, but the lengths of the thick and thin filaments do not change.
  • Cross-Bridge Cycle: Sequence of events that occurs between the time a cross-bridge binds to a thin filament, moves, and then is set to repeat the process. Each cross-bridge undergoes its own cycle of movement independently of other cross-bridges.

• Chemical and mechanical events:
  1. binding of energized myosin cross-bridge (M) to a thin filament actin molecule (A)
  M . ADP . Pi + A → A . M . ADP . Pi
  2. The binding of energized myosin to actin triggers the release of the strained conformation of the energized cross-bridge, which produces the movement of the bound cross-bridge (sometimes called the power stroke) and the release of Pi and ADP:
  A . M . ADP . Pi → A . M + ADP + Pi
  3. The binding
  of a new molecule of ATP to myosin breaks the link between actin and myosin:
  A . M + ATP → M . ATP + A
  4.Following the dissociation of actin and myosin, the ATP bound to myosin is hydrolyzed by myosin-ATPase, thereby re-forming the energized state of myosin and returning the cross- bridge to its pre-power-stroke position:
  M . ATP → M . ADP . P_i

• Functions of ATP in Skeletal Muscle Contraction
  Hydrolysis of ATP by the Na^+/K^+-ATPase in the plasma membrane maintains Na^+ and K^+ gradients, which allows the membrane to produce and propagate action potentials.Hydrolysis of ATP by the Ca^{2+}-ATPase in the sarcoplasmic reticulum provides the energy for the active transport of calcium ions into the reticulum, lowering cytosolic Ca^{2+} to prerelease concentrations, ending the contraction, and allowing the muscle fiber to relax.Hydrolysis of ATP by myosin-ATPase energizes the cross-bridges, providing the energy for force generation.Binding of ATP to myosin dissociates cross-bridges bound to actin, allowing the bridges to repeat their cycle of activity.

• Review

  • Contraction: activation of force generation in a muscle fiber; relaxation refers to turning off the force-generating mechanisms and allowing a decrease in tension.
  • Alpha motor neurons: the neurons that innervate skeletal muscle fibers; one motor neuron innervates many muscle fibers, forming a motor unit.
  • Neuromuscular junction: formed from branches of a motor neuron axon that contact a muscle fiber at a region of the fiber called a motor end plate
  • Acetylcholine is the neurotransmitter released by motor neurons; it binds to receptors on the motor end plate of the muscle membrane, causing depolarization (end plate potential).
  • A single action potential in a motor neuron is sufficient to produce an action potential in a skeletal muscle fiber.
  • Signaling at the neuromuscular junction can be disrupted by a number of toxins, drugs, and diseases; overstimulation is normally prevented by acetylcholinesterase.
  • Excitation–contraction coupling: sequence of events beginning with action potentials and leading to contraction of a skeletal muscle fiber:
  • Cytosolic Ca^{2+} concentration is increased following electrical excitation of a fiber.
    Ca^{2+} binds to troponin, which causes tropomyosin to move away from (unblock) the myosin-binding sites on actin.
  • Cross-bridges bind to the thin filaments.
  • Relaxation occurs when Ca^{2+} is pumped back into the sarcoplasmic reticulum, allowing troponin and tropomysin to resume their blocking action.
  • Sliding-filament mechanism: The thin filaments are propelled toward the center of a sarcomere by movements of the myosin cross-bridges that bind to actin, thereby shortening the fiber.
  • The cross-bridges undergo repeated cycles during a contraction, each cycle producing only a small increment of movement.
  • ATP has two roles in the cross-bridge cycle: an allosteric function that induces cross-bridges to detach from actin

Mechanics of Single-Fiber Contraction

• Muscle tension: Force exerted by a contracting muscle on an object.

• Load: Force exerted by an object on a muscle.

• Isometric contraction: Muscle develops tension but does not change length.

• Isotonic contraction: Muscle changes length while the load remains constant; can be concentric (shortening) or eccentric (lengthening).

• Twitch: Mechanical response of a muscle fiber to a single action potential.

• Latent period: Time interval between action potential and tension increase.

• Fast-twitch fibers: Short contraction times.

• Slow-twitch fibers: Longer contraction times.

• Summation: Increase in tension from successive action potentials during mechanical activity.

• Tetanus (tetanic contraction): Maintained contraction in response to repetitive stimulation; can be unfused or fused.

• Length–Tension Relation: Influenced by elastic springlike titin; maximum tension when fibers are at optimal length (L_0).

• Review

  • Contraction: refers only to activation of the cross-bridge cycle
  • Tension: force exerted on an object by a contracting muscle
  • Load: force exerted on a muscle by an object (its weight)
  • Whether there is an accompanying change in muscle length depends upon the external forces acting on the muscle.
  • Types of contractions:
    >* Isometric contraction: the muscle generates tension but does not change length
    >* Isotonic contraction: the muscle either shortens (concentric contraction) or lengthens (eccentric contraction) while moving a load that remains constant
  • Twitch contraction: mechanical response of a muscle fiber to a single action potential
  • Latent period: short interval following an action potential before tension rises in a muscle fiber during which events of excitation–contraction coupling are beginning
  • Fiber types:
    >* Fast-twitch fibers have very short contraction times (interval from beginning of latent period to the time of peak tension development); slow-twitch fibers have longer contraction times.
    >* Increasing the frequency of action potentials in a muscle fiber increases the mechanical response (tension or shortening) up to the level of maximal tetanic tension (maintained contraction in response to repetitive stimulation).
  • Maximum isometric tetanic tension: produced at optimal length (L_0) of a sarcomere
  • Stretching a fiber beyond L0 or decreasing it below L0 decreases the tension generated, because of reduced cross-bridge access to thin filaments at short and long sarcomere lengths.
  • The velocity of muscle fiber shortening decreases with increases in load. Maximum velocity occurs at zero load.

Skeletal Muscle Energy Metabolism

• ATP functions in muscle contraction and relaxation.

• Three ways a muscle fiber can form ATP:
  phosphorylation of ADP by creatine phosphate (CP)
  >* oxidative phosphorylation of ADP in the mitochondria Phosphorylation of ADP by the glycolytic pathway in the cytosol At moderate levels of muscular activity, most of the ATP used for muscle contraction is formed by oxidative phosphorylation

  • Creatine phosphate: Rapid ATP formation at the onset of contractile activity, catalyzed by creatine kinase, reversible reaction:
    creatine + ATP ↔ CrP + ADP
  • Oxidative phosphorylation: Dominant ATP source at moderate activity levels. Blood glucose and fatty acids are the contributors as exercise period increases.
  • Glycolysis: Contributes significantly at high exercise intensity without oxygen. Is the breakdown of glucose.
  • Oxygen debt: Increased oxygen consumption after exercise to restore energy reserves.

• Muscle Fatigue causes include metabolic changes: decrease in ATP concentration, increases in the concentrations of ADP, Pi, Mg2+ , H+(from lactic acid), and oxygen free radicals. All of these mechanisms have been demonstrated to be important under particular experimental conditions, but their exact relative contributions to acute fatigue in intact human muscle have yet to be resolved. Also decrease the rate of Ca^{2+} release, reuptake, and storage by the sarcoplasmic reticulum, decrease the sensitivity of the thin filament proteins to activation by Ca^{2+}, directly inhibit the binding and power-stroke motion of the myosin cross-bridges.

• Central Command Fatigue occurs when the the appropriate regions of the cerebral cortex fail to send excitatory signals to the motor neurons.

• Review

  • Muscle fibers form ATP by 3 mechanisms:
    transferred of phosphate from creatine phosphate to ADP
    >* oxidative phosphorylation of ADP in mitochondria
    phosphorylation of ADP in the glycolytic pathway
    The fuel consumed by skeletal muscle changes with the duration of activity during low-intensity exercise.
    >* beginning of exercise: muscle glycogen is the major fuel consumed
    continued exercise: glucose and fatty acids from the blood provide most of the fuel prolonged exercise: fatty acids become progressively more important
  • When exercise intensity is sufficiently high, glycolysis begins to contribute an increasingly large fraction of the total ATP generated.
  • Muscle fatigue results from several factors:
    >* a decrease in ATP concentration increases in the cellular concentrations of ADP, Pi, Mg^{2+} , H^+, and oxygen free radicals
    >* These changes have effects such as decreasing Ca^{2+} uptake and storage by the sarcoplasmic reticulum, decreasing the sensitivity of the thin filaments to Ca^{2+} , and inhibiting the binding and power-stroke motion of the cross-bridges.

Types of Skeletal Muscle Fibers

• Classified by maximal shortening velocities (fast or slow-twitch) and ATP production pathway (oxidative or glycolytic).

• Fast-twitch fibers (type 2): Myosin with high ATPase activity (2A and 2X subtypes).

  • Slow-twitch fibers (type 1): Myosin with low ATPase activity.
  • Oxidative fibers: Numerous mitochondria and high capacity for oxidative phosphorylation; surrounded by many blood vessels, contain myoglobin (red muscle fibers).
  • Glycolytic fibers: Few mitochondria, high concentration of glycolytic enzymes, large glycogen store (white muscle fibers).
  • Slow-oxidative fibers (type 1): Low myosin-ATPase activity and high oxidative capacity.
  • Fast-oxidative-glycolytic fibers (type 2A): High myosin-ATPase activity, high oxidative capacity, and intermediate glycolytic capacity.
  • Fast-glycolytic fibers (type 2X): High myosin-ATPase activity and high glycolytic capacity.
  • fiber types generate different amounts of isometric tension. Slow-oxidative fibers generate the least tension, fast-oxidative-glycolytic fibers are intermediate, and fast-glycolytic fibers generate the greatest tension.
  • Fast-glycolytic fibers fatigue rapidly, whereas slow-oxidative fibers are very resistant to fatigue. Fast-oxidative-glycolytic fibers have an intermediate capacity to resist fatigue.

• Review

  • Three types of skeletal muscle fibers can be distinguished by their maximal shortening velocities and the predominant pathway they use to form ATP:
    >* slow-oxidative fibers (type 1)
    >* fast-oxidative-glycolytic fibers (type 2A)
    fast-glycolytic fibers (type 2X)
    Differences in maximal shortening velocities are due to different myosin enzymes with high or low ATPase activities, giving rise to fast and slow fibers.Oxidative fibers have many mitochondria and possess a high amount of the oxygen-binding protein myoglobin.Glycolytic fibers have few mitochondria but have a high concentration of glycolytic enzymes and little or no myoglobin.Fast-glycolytic fibers have a larger average diameter than oxidative fibers and therefore produce greater tension, but they also fatigue more rapidly.All muscle fibers in a single motor unit belong to the same fiber type; most muscles contain all three types.

Whole-Muscle Contraction

• Muscles are made up of many muscle fibers organzied into motor units.

• Motor unit: A motor neuron and all the muscle fibers it innervates, same fiber type.

• Muscle tension: Amount of tension developed by each fiber and number of fibers contracting.

  • Recruitment: Increasing the number of active motor units in a muscle.
  • Smaller motor neurons are recruited first, followed by larger motor neurons.

• Adaptation to exercise influences the properties of muscle
  Atrophy-denervation: If the neurons to a skeletal muscle are destroyed
  Atrohpy-disuse: If the muscle if not used for a long time.

  • Low-Intensity Exercise: (aerobic exercise) Increases the number of mitochondria in all muscle fibers and a shift in myosin composition of fast fibers from type 2X to type 2A.. All these changes lead to an increase in the ability to sustain muscle contraction through oxidative metabolism and thus increased capacity for endurance activity with a minimum of fatigue.
  • High-Intensity Exercise: Short duration. primarily the fast-twitch fibers are recruited. These fibers undergo an increase in diameter (hypertrophy) due to satellite cell activation and increased synthesis of actin and myosin filaments, which form more myofibrils. The myosin expressed in fast fibers shifts from type 2A toward the faster and more powerful type 2X. In addition, glycolytic activity is increased by increasing the synthesis of glycolytic enzymes.
  • Lever Action
    Flexion contraction of limb a joint.
    Extension Straightening of limb a joint..

• Review

  • The tension produced by whole-muscle contraction depends on the amount of tension each fiber develops and the number of active fibers in the muscle.
  • Muscles that produce delicate movements have a small number of fibers per motor unit; large, powerful muscles have much larger motor units.
  • Fast-glycolytic motor units not only have large-diameter fibers but also tend to have large numbers of fibers per motor unit.
  • Recruitment: process by which increases in muscle tension are controlled primarily by increasing the number of active motor units in a muscle
    order of recruitment: slow-oxidative motor units, then fast-oxidative-glycolytic motor units, then fast-glycolytic motor units (only during very strong contractions)
    Increasing motor-unit recruitment increases the velocity at which a muscle will move a given load.
  • Exercise can alter a muscle’s strength and susceptibility to fatigue.Movement around a joint generally involves groups of antagonistic muscles; some flex a limb at the joint (flexion) and others extend the limb (extension).The lever action of muscles and bones generally requires muscle tension far greater than the load in order to sustain
    a load in an isometric contraction, but the lever system produces a shortening velocity at the end of the lever arm that is greater than the muscle-shortening velocity.

Skeletal Muscle Disorders

• Muscle Cramps
  Involuntary tetanic contraction of skeletal muscles produce muscle cramps may be partly related to electrolyte imbalances in the extracellular fluid surrounding both the muscle and nerve fibers.

• Hypocalcemic Tetany
  The involuntary tetanic contraction of skeletal muscles that occurs when the extracellular Ca^{2+} concentration decreases to about 40% of its normal value
  results from Low extracellular Ca2+ (hypocalcemia) increases the opening of Na^{+} channels in excitable membranes, leading to membrane depolarization and the spontaneous firing of action potentials.

• Muscular Dystrophy
  Muscular dystrophy is a genetic disorder that results from defects of muscle-membrane-stabilizing proteins such as dystrophin. Muscles of individuals with Duchenne muscular dystrophy progressively degenerate with use.
  It can be treated with therapies to insert the normal gene into dystrophic muscle cells.

• Myasthenia Gravis
  Autoimmune disorder in which destruction of ACh receptors of the motor end plate causes progressive loss of the ability to activate skeletal muscles. can be treated with administer acetylcholinesterase inhibitors

Smooth and Cardiac Muscle

• All smooth muscles lack the cross-striated banding pattern found in skeletal and cardiac fibers (which makes them appear “smooth”), and the nerves to them are part of the autonomic division of the nervous system rather than the somatic division. Thus, smooth muscle is not normally under direct voluntary control.
• Review:
  Smooth muscle cells: spindle-shaped, non-striated cells with a single nucleus and capable of cell division contain actin and myosin filaments but no sarcomeres and contract by a sliding-filament mechanism dense bodies: cytoplasmic structures functionally similar to Z lines in skeletal muscle fibers; anchor the thin filaments isometric tension developed by smooth muscle fibers varies with fiber length as in skeletal muscle, but maximum tension is generated over a wider range.

Smooth Muscle Contraction and Its Control

• Cross-bridge Activity is controlled by a Ca^{2+}-regulated enzyme that phosphorylates myosin, only the phosphorylated form of smooth muscle myosin can bind to actin and undergo cross-bridge cycling.
• To relax a contracted smooth muscle, myosin must be dephosphorylated because dephosphorylated myosin is unable to bind to actin This dephosphorylation is mediated by the enzyme myosin light-chain phosphatase, which is continuously active in smooth muscle during periods of rest and contraction
• Two sources of Ca^{2+} contribute to the increase in cytosolic Ca^{2+} that initiates smooth muscle contraction: (1) the sarcoplasmic reticulum and (2) extracellular Ca^{2+} entering the cell through plasma membrane Ca^{2+} channels
• Membrane activation includes spontaneous electrical activity, nerves, hormones, and local factors

*Types of Smooth Muscle:
Single Unit: The muscle cells in single-unit smooth muscle undergo synchronous activity, both electrical and mechanical. Some of the cells in single-unit smooth muscle are pacemaker cells that spontaneously generate action potentials.
Multiunit: Multiunit smooth muscles have no or few gap junctions.

• * * Review:An increase in cytosolic Ca^{2+} leads to a chain of events that results in phosphorylation of light chains of smooth muscle myosin by myosin light-chain kinase. Only phosphorylated myosin can bind to actin and undergo cross-bridge cycling.Two sources of the cytosolic calcium ions that initiate smooth muscle contraction are the sarcoplasmic reticulum and extracellular Ca^{2+} .smooth muscle tone: a low level of basal cross-bridge activity at resting, low concentrations of cytosolic Ca^{2+} in the absence of external stimuli. The strength of smooth muscle contraction varies with the increase in cytosolic Ca^{2+} and is influenced by multiple stimuli including:
  hormones autonomic neurotransmitterslocal metabolic conditionsstretchspontaneous electrical activity in the plasma membrane.Most smooth muscle cells can generate action potentials in the plasma membrane upon membrane depolarization. Pacemaker potentials: spontaneously generated action potentials in the absence of any external input; occur in some smooth muscle cells. Slow waves are a pattern of spontaneous, periodic depolarizations of the membrane potential seen in some smooth muscle pacemaker cells, particularly in the gastrointestinal tract. smooth muscle cells do not have a specialized end-plate region Multiple smooth muscle cells may be influenced by neurotransmitters released from a single neuron ending, and a single smooth muscle cell may be influenced by neurotransmitters from more than one neuron neurotransmitters may have either excitatory or inhibitory effects on smooth muscle contraction by increasing or decreasing cytosolic Ca^{2+* * * Smooth muscles can be classified broadly as single-unit or multiunit smooth muscles: Single-unit: cells undergo pacemaker-linked synchronous activity because of gap junction connections sensitive to stretch like that which occurs in expandable hollow organs such as the stomach multiunit: each fiber responds independently due to few if any gap junctions linking them; richly innervated by autonomic nerves

Cardiac Muscle

• Cardiac muscle combines properties of both skeletal and smooth muscle
• excitation–contraction coupling in Cardiac muscle involvesEntry of a small amount of Ca^{2+} through L-type Ca^{2+} channels triggers opening of ryanodine receptors that release a larger amount of Ca^{2+}$$ from the sarcoplasmic reticulum.Ca activates the thin filament and cross-bridge cycling as in skeletal muscle.Cardiac contractions and action potentials are prolonged, tetany does not occur, and both the strength and frequency of contraction are modulated by autonomic neurotransmitters and hormones.