ELEC ENG 3BB3:

Cellular Bioelectricity

Notes for Lecture #28Friday, March 24, 2006

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11. SKELETAL MUSCLE

We will look at:

Muscle structure

Muscle contraction

Structure of the myofibril

Sliding filament theory

Excitation-contraction

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Muscle structure:skeletal muscle is made up ofmuscle fiberseach fiber isa single cellthe contraction ofa fiber is achieved by the motor proteins actin & myosin whichform fibrils

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Muscle structure (cont.):Each fibril is surrounded by:

a sarcoplasmic reticulum (SR), which stores Ca2+ for triggering muscle fiber contraction, andthe transverse tubules system (TTS), which ensures that action potentials propagate deep into the fiber.

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Muscle contraction:A muscle fiber responds to a single neural input with a contractile twitch. A fast train of stimuli will twitches that sum together; above the fusion frequency, the fiber will be locked in a state referred to as tetanus.

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Muscle contraction (cont.):Under physiological conditions, different motor units in a muscle bundle will receive asynchronous motor neuron input at rates below the fusion frequency to produce a sustained muscle contraction.Muscle fibers can be roughly grouped into two classes based on their contraction speed, fast twitch and slow twitch.Muscles are always made up of some combination of fast and slow twitch fibers.

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Muscle contraction (cont.):1. Fast twitch– large fibers, for greater contraction strength

– extensive sarcoplasmic reticulum for rapid release of Ca2+

– large amounts of glycolytic enzymes

– less extensive blood supply

– fewer mitochondria

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Muscle contraction (cont.):2. Slow twitch– smaller fibers

– innervated by smaller nerve fibers (axons)

– more extensive blood vessel system

– more mitochondria

– large amounts of myoglobin, speeding oxygen transport

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Muscle contraction (cont.):The tension produced by a contraction also depends on i) the velocity of the contraction, and ii) the length of the muscle, as illustrated below.

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Structure of the myofibril:Myofibrils are a specialized arrangement of thick myosin filaments and thin actin filaments.

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Structure of the myofibril (cont.):The arrangement of myosin and actin filaments in the myofibril produces a banded pattern when observed with a light microscope. Each repeating unit (Z-Z) is referred to as a sarcomere.

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Structure of the myofibril (cont.):Myosin filaments have specialized regions to produce movements against the actin filaments.

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Structure of the myofibril (cont.):In the regions where they overlap, each myosin (thick) filament is surrounded by six actin (thin) filaments, and each actin filament is surrounded by three myosin and three actin filaments, in an alternating fashion.

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Structure of the myofibril (cont.):

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Muscle structure (cont.):The structure of thick myosin filaments shown on the previous slide can be explain by the aggregation of myosin molecules as illustrated below.

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Sliding filament theory:The sliding filament theory suggests that contraction is generated by movement of the myosin filaments against the actin filaments.

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Sliding filament theory (cont.):The sliding filament theory is consistent with the tension versus length relationship of muscle undergoing isometric contraction.

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Sliding filament theory (cont.):

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Sliding filament theory (cont.):

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Excitation-contraction:Steps in muscle fiber contraction1. Motor neuron action potential2. Action potential propagation along motor axon

(myelinated fiber)3. Transmission of acetylcholine (ACh) at

neuromuscular junctions (synapses)4. Action potential generation in muscle fiber5. Release of Ca2+ from sarcoplasmic reticulum

initiates attractive forces between actin & myosin filaments, causing them to slide alongside each other ⇒ muscle contraction

6. Return of Ca2+ to sarcoplasmic reticulum, ending muscle contraction

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Excitation-contraction (cont.):The TTS and SR are crucial for synchronized contraction of all fibrils in skeletal myocytes and mammalian cardiac myocytes.

(Song et al., Ann. N.Y. Acad. Sci. 2005).

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Excitation-contraction (cont.):Organization of key channel and transporter proteins and SR structures, including the junctional SR (JSR), near the TT —

(Song et al., Ann. N.Y. Acad. Sci. 2005).

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Excitation-contraction (cont.):

The release of Ca2+ to trigger contraction of fibrils is facilitated by two different types of Ca2+ channels:1. dihydropyridine receptors (DHPRs) or L-

type Ca2+ channels, and2. ryanodine receptors (RyRs).

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Excitation-contraction (cont.):L-type Ca2+ channels are voltage-gated and appear on the TT and sarcolemmal(SL) membrane. These are opened by Na+ action potentials, allowing Ca2+ to flow into the intracellular space near the JSR.Reception of Ca2+ by RyRs opens up Ca2+ channels in the JSR membrane allowing release of Ca2+ from the SR. This leads to a positive feedback loop of Ca2+ release, triggering fibril contraction.