MUSCLE PHYSIOLOGYAss. Prof. Dr. Emre Hamurtekin

EMU Faculty of Pharmacy

SKELETAL MUSCLE

STRUCTURAL PROPERTIES

STRUCTURAL PROPERTIES

STRUCTURAL PROPERTIES

STRUCTURAL PROPERTIES

SARCOTUBULAR SYSTEM• T system and sarcoplasmic

reticulum• T system of transverse tubules

is continous with the sarcolemma

• The SR has enlarged terminal cisterns at the junctions between the A and I bands.

• Triad• T system provides a path for

the rapid transmission of action potential

• SR is an important store of Ca

SARCOTUBULAR SYSTEM

ELECTRICAL and ION CHARACTERISTICS of SKELETAL MUSCLE

• Resting membrane potential: -90 mV• Action potential lasts: 2-4 ms• Conducted along the muscle fiber : 5 m/s• Ion distribution is similar to that across the

nerve cell membrane.

CONTRACTILE RESPONSES

• Muscle twitch: A brief contraction folllowed by relaxation which is caused by a single action potential.

MOLECULAR BASIS OF CONTRACTION• In resting muscle:

Troponin I covers the sites where myosin heads interact with actin Myosin head contains tightly bound ADP

• Step 1: Following an action potential, cytosolic Ca increases and binds to Troponin C

• Step 2: Weakening of Troponin I interaction with actin and myosin-actin cross bridges occur.

• Step 3: Upon formation of the cross-bridge, ADP is released.• Step 4: ADP release causes a conformational change and myosin head

moves the thin filament (power stroke).• Step 5: ATP binds to the free site on the myosin. This leads to a

detachment of the myosin head from the thin filament.• Step 6: ATP is hydrolyzed and cycle is completed.

MOLECULAR BASIS OF CONTRACTION

• Excitation-contraction coupling: The process that a depolarization of a muscle fiber initiates a contraction

• Ca is reduced in the muscle cell by SERCA and this causes a cessation of interaction between actin and myosin

• Pumping of the Ca back into the sarcoplasmic reticulum causes relaxation

TYPES OF CONTRACTION

ISOMETRIC ISOTONIC(same length) (same tension)

SUMMATION OF CONTRACTIONS

• Contractile mechanism does not have a refractory period.• Summation of contraction: Additional contractile

response that is added to the already present contraction.

• Tetanic contraction (tetanus): Because of the activation of contractile mechanism occurs repeatedly before any relaxation occurs, individual responses fuse into one continuous contraction.

• Tetanic contraction:– Complete tetanus– Incomplete tetanus

SUMMATION OF CONTRACTIONS

MOTOR UNIT

• Each single motor neuron and the muscle fibers it innervates constitute a motor unit.

• The number of muscle fibers in a motor unit varies.

CARDIAC MUSCLE

MORPHOLOGY• The striations are

similar to those in skeletal muscle.

• Z-lines are present.

• There are large numbers of mitochondria.

• The muscle fibers branch and interdigitate.

• Intercalated disks

Muscle fiber resmi

MORPHOLOGY

• Along the sides of the muscle fibers next to the disks, the cell membranes form gap junctions.

• Cardiac muscle function as if it was a syncytium: Intercalated disk Gap junctions

• T-system in cardiac muscle is located at Z-lines (not at the A - I junction).

ELECTRICAL PROPERTIES

• The resting membrane potential: -80 mV.• A plateau is present before the membrane

potential returns to the baseline.• Cardiac myocytes contain at least 2 types of Ca

channels (T- and L-types), but the Ca current is mostly due to opening of slower L-type Ca channels.

ELECTRICAL PROPERTIESPhase 0

initial rapid depolarization and the overshoot

Phase 1

the initial rapid repolarization

Phase 2

prolonged plateau

Phase 3 to Phase 4final repolarization to resting membrane potential

opening of voltage-gated Na channels.

closure of Na channels and opening of one type of K channel.

slower but prolonged opening of voltage-gated Ca channels.

closure of Ca channels and a slow delayed increase of K efflux through various types of K channels.

MECHANICAL PROPERTIES & METABOLISM

• The contractile response of cardiac muscle lasts about 1.5 times as long as the action potential.

• The cardiac muscle can’t be tetanized!!!• Abundant blood supply, numerous mitochondria, high

content of myoglobin.• Normally less than 1% of the total energy is provided by

anaerobic metabolism.• Under basal conditions caloric needs of the heart are

provided by,– 35% by carbohydrate– 5% by ketones and amino acids– 55% by fat

SMOOTH MUSCLE

MORPHOLOGY

• No visible cross-striations.• Actin & myosin II are present and slide on

each other to produce contraction .• Instead of Z-lines, there are dense bodies.• Contains tropomyosin but troponin is absent.• Sarcoplasmic reticulum is less extensive.• Contain few mitochondria.

MORPHOLOGY

TYPES

• A) Unitary (visceral) smooth muscleB) Multiunit smooth muscle

• Unitary (visceral) smooth muscle– i.e. intestine, uterus, ureter– occurs in large sheets– has many low-resistance gap-junctional connections (syncytial

function)• Multiunit smooth muscle

– i.e. iris of the eye– individual units (few or no gap junctional bridges)– Each multiunit smooth muscle cell has endings of nerve fibres.

TYPES

ELECTRICAL & MECHANICAL ACTIVITY

• Unitary smooth muscle is characterized by the instability of its membrane potential.

• Continuous, irregular contractions (tonus)• Resting potential: from -20 mV to -65 mV.• Excitation-contraction coupling in unitary

smooth muscle is a very slow process.• Contractions of multiunit smooth muscle are

more discrete, fine and localized than unitary smooth muscle contractions.

CONTRACTION & RELAXATION

• Source of Ca increase in unitary smooth muscle:– influx through voltage or ligand-gated plasma

membrane channels.– efflux from intracellular stores through the RyR– efflux from intracellular stores through the IP3

receptor Ca channel. • The lack of troponin: myosin must be

phosphorylated for activation of myosin ATPase.– Calmodulin-dependent myosin light chain kinase

CONTRACTION & RELAXATION

CONTRACTION & RELAXATION

CONTRACTION & RELAXATION

Contraction

Dephosphorylation of myosin by myosin light chain

phosphatase

Relaxation, or sustained contraction due to the latch

bridge and other mechanisms

CONTRACTION & RELAXATION

• Unitary smooth muscle contracts when stretched in the absence of any extrinsic innervations unlike other types of muscle.

• Intestinal smooth muscle preparation:Norepinephrine (relaxation) X acetylcholine (contraction)

• NO-nitric oxide- (released from endothelial cells) leads to relaxation of blood vessel smooth cell.

THE END