Muscle Physiology Lecture 1

Front 1

What are DHPR's and what is their role?

Back 1

V-gated Ca2+ channels located in the T-tubule.
Closely associated with RyRs
Open with depolarization and activate RyRs

Front 2

What are RyRs and what is their role?

Back 2

Macromolecular proteins in the junctional SR.
Function as Ca2+ release channels.
Span the gap between SR and T-tubules.
Mechanically activated by DHPRs in T-Tubules.

Front 3

Describe the arrangement of myofilament proteins.

Back 3

Lattice of thick (myosin) and thin (actin) filaments arranged in sarcomeres.

Front 4

Z-lines connect __?

Back 4

Actin filaments

Front 5

A-bands?

Back 5

Dark A-bands of sarcomere indicate overlap of myofilaments.

Front 6

Contraction in muscle is produced by sliding of ___ past each other causing the ___ to shorten.

Back 6

Myofilaments
Sarcomere

Front 7

Myosin globular heads bind to ?

Back 7

Actin

Front 8

What provides the E for the power stroke in muscle contraction?

Back 8

ATP hydrolysis

Front 9

What triggers contraction in skeletal muscle?

Back 9

A rise in the concentration of Calcium inside the myofibril.

Front 10

What property do all muscle types have in common?

Back 10

All muscles TRANSDUCE chemical or electrical commands into mechanical responses. (contraction)

Front 11

What are DHPR's and what is their role?

Back 11

V-gated Ca2+ channels located in the T-tubule.
Closely associated with RyRs
Open with depolarization and activate RyRs

Front 12

What are RyRs and what is their role?

Back 12

Macromolecular proteins in the junctional SR.
Function as Ca2+ release channels.
Span the gap between SR and T-tubules.
Mechanically activated by DHPRs in T-Tubules.

Front 13

Describe the arrangement of myofilament proteins.

Back 13

Lattice of thick (myosin) and thin (actin) filaments arranged in sarcomeres.

Front 14

Z-lines connect __?

Back 14

Actin filaments

Front 15

A-bands?

Back 15

Dark A-bands of sarcomere indicate overlap of myofilaments.

Front 16

Contraction in muscle is produced by sliding of ___ past each other causing the ___ to shorten.

Back 16

Myofilaments
Sarcomere

Front 17

Myosin globular heads bind to ?

Back 17

Actin

Front 18

What provides the E for the power stroke in muscle contraction?

Back 18

ATP hydrolysis

Front 19

What triggers contraction in skeletal muscle?

Back 19

A rise in the concentration of Calcium inside the myofibril.

Front 20

What property do all muscle types have in common?

Back 20

All muscles TRANSDUCE chemical or electrical commands into mechanical responses. (contraction)

Front 21

Broad functions of muscle types:
1) Skeletal
2) Cardiac
3) Smooth

Back 21

1) Posture, Voluntary Movement
2) Rhythmic contraction to maintain BP
3) Peristalsis, Vascular Tone, Sphincter Muscles

Front 22

What physiological properties should be considered regarding the suitability of a particular muscle type for its function?

Back 22

1) Velocity of contraction
2) Duration of contraction
3) Fatigability of contraction

Front 23

Skeletal muscle-
Velocity?
Duration?
Fatigability?

Back 23

Rapid force development.
Relatively long duration.
Variable fatigue.

Front 24

Cardiac muscle-
Velocity?
Duration?
Fatigability?

Back 24

Rapid force development.
Very short duration.
No fatigue.

Front 25

Smooth Muscle-
Velocity?
Duration?
Fatigability?

Back 25

Slow force development and range of forces.
Some long duration.
No fatigue.

Front 26

How does electrical excitation occur in skeletal muscle?

Back 26

Electrical excitation is achieved here by motor nerve activation.

Front 27

How does electrical excitation occur in cardiac muscle?

Back 27

Initiated from SA node.
Cells electrically coupled via gap junctions.
Nerves only MODULATE contraction.

Front 28

How does electrical excitation occur in smooth muscle?

Back 28

Can be excited by nerves or by electrical coupling to neighboring cells.

Front 29

ECC = ?

Back 29

Excitation- Contraction Coupling
How electrical excitation leads to rise in Calcium resulting in contraction.

Front 30

The process of ECC is ___ amongst the 3 basic muscle types.

Back 30

Different

Front 31

How is an action potential produced in skeletal muscle from the release of ACh at the motor end plate?

Back 31

ACh causes activation of nAChRs at postsynaptic membrane of the muscle causing EPP causing AP if threshold is reached.

Front 32

This is more organized in skeletal muscles than in cardiac muscles.

Back 32

Myofibrils

Front 33

What are the 3 noticeable features of skeletal muscle ultrastructure?

Back 33

1) T-Tubules
2) Sarcoplasmic Reticulum
3) Organization of Myofibrils

Front 34

What is the function of T-tubules in skeletal muscle?

Back 34

Invaginations of muscle sarcolemma at A-I junctions (Z-lines in cardiac) where AP is projected down into muscle.

Front 35

This is much more extensive in skeletal muscle than cardiac muscle.

Back 35

Sarcoplasmic Reticulum

Front 36

What is the function of the SR in skeletal muscle?

Back 36

Storage of Calcium for contraction.

Front 37

What is a triad?

Back 37

T-tubules form tight junctions with two terminal cisternae.

Front 38

Cisternae

Back 38

end of sarcoplasmic reticulum

Front 39

What is the equivalent structure to a triad called in cardiac muscle?

Back 39

Dyad
Only 1 terminal cisternae adjoining T-tubules.

Front 40

These are the "feet" connecting the T-tubules to the SR.

Back 40

Ryanodine Receptors (RyRs)

Front 41

Broad functions of muscle types:
1) Skeletal
2) Cardiac
3) Smooth

Back 41

1) Posture, Voluntary Movement
2) Rhythmic contraction to maintain BP
3) Peristalsis, Vascular Tone, Sphincter Muscles

Front 42

What physiological properties should be considered regarding the suitability of a particular muscle type for its function?

Back 42

1) Velocity of contraction
2) Duration of contraction
3) Fatigability of contraction

Front 43

Skeletal muscle-
Velocity?
Duration?
Fatigability?

Back 43

Rapid force development.
Relatively long duration.
Variable fatigue.

Front 44

Cardiac muscle-
Velocity?
Duration?
Fatigability?

Back 44

Rapid force development.
Very short duration.
No fatigue.

Front 45

Smooth Muscle-
Velocity?
Duration?
Fatigability?

Back 45

Slow force development and range of forces.
Some long duration.
No fatigue.

Front 46

How does electrical excitation occur in skeletal muscle?

Back 46

Electrical excitation is achieved here by motor nerve activation.

Front 47

How does electrical excitation occur in cardiac muscle?

Back 47

Initiated from SA node.
Cells electrically coupled via gap junctions.
Nerves only MODULATE contraction.

Front 48

How does electrical excitation occur in smooth muscle?

Back 48

Can be excited by nerves or by electrical coupling to neighboring cells.

Front 49

ECC = ?

Back 49

Excitation- Contraction Coupling
How electrical excitation leads to rise in Calcium resulting in contraction.

Front 50

The process of ECC is ___ amongst the 3 basic muscle types.

Back 50

Different

Front 51

How is an AP produced in skeletal muscle from the release of ACh at the motor end plate?

Back 51

ACh ->
Activation of nAChRs at postsynaptic membrane of the muscle ->
EPP ->
AP if threshold is reached

Front 52

This is more organized in skeletal muscle than in cardiac muscle.

Back 52

Myofibril organization.

Front 53

What are the 3 noticeable features of skeletal muscle ultrastructure?

Back 53

1) T-Tubules
2) Sarcoplasmic Reticulum
3) Organization of myofibrils

Front 54

What is the function of T-Tubules in skeletal muscle?

Back 54

Invaginations of muscle sarcolemma at A-I junctions (Z-lines in cardiac) where AP is projected down into muscle

Front 55

What is the function of Sarcoplasmic Reticulum in skeletal muscle?

Back 55

Store of Calcium for contraction.

Front 56

What is a triad?

Back 56

T-Tubules form tight junctions with two terminal cisternae.

Front 57

Cisternae

Back 57

End of Sarcoplasmic Reticulum

Front 58

What is the structure equivalent to a triad in cardiac muscle?

Back 58

Dyad
Only 1 terminal cisternae adjoining T-Tubules.

Front 59

These "Feet" connect the T-Tubule to the Sarcoplasmic Reticulum.

Back 59

RyRs

Front 60

Where are RyRs located?
What is their function?

Back 60

Location- spanning the gap between the SR and T-Tubules.
Function- Calcium release channels. Pass calcium from SR to T-Tubules.

Front 61

What are the important dimensions of a RyRs?

Back 61

Extends 12 nm from SR membrane.
Gap between SR and T-Tubule is 15 nm so RyRs goes almost the entire distance.

Front 62

What type of receptor is a Dihydropyridine Receptor?

Back 62

DHPRs
L-Type Calcium Channels

Front 63

What is the structure and location of DHPRs?

Back 63

Arranged in clusters of 4.
Positioned over every other RyRs. (Not random!)

Front 64

What is the overall ratio of RyRs to DHPRs?

Back 64

1:2

Front 65

What is the mechanism of ECC coupling in skeletal muscle?

Back 65

The DHPR and RyRs are mechanically coupled.

Front 66

How does an AP in the T-Tubule lead to Calcium release?

Back 66

Deplarization in T-Tubule ->
Opens DHPRs (mechanically coupled to RyRs) ->
Opens RyRs ->
Calcium Release

Front 67

What part of the DHPR interacts with the RyR?

Back 67

II-III Intracellular Loop

Front 68

Is Calcium entry through DHPRs required to trigger Calcium release from the RyR?

Back 68

NO. Its the physical interaction of the proteins that matters, not the Calcium entry.

Front 69

In what sense is EC coupling in skeletal muscle V-Dependent?

Back 69

We have to depolarize to open DHPRs which in turn open RyRs.

Front 70

In what sense is EC coupling in skeletal muscle not V-Dependent?

Back 70

Once DHPRs are open.
With large depolarizations, we -> Nernst potential for Calcium. It becomes more and more positive inside the cell. The driving force for Calcium decreases, but is irrelevant because Calcium entry is not required.

Front 71

Because Calcium entry is not required for contraction in skeletal muscle, this implies that ____ is the primary source of Calcium for contraction.

Back 71

Sarcoplasmic Reticulum
(We dont care about Calcium coming into the cell because its already in the cell in the SR.)

Front 72

Not all RyRs are coupled with DHPRs. How are these uncoupled RyRs activated?

Back 72

Calcium induced Calcium release.

Front 73

How does Calcium induced Calcium release work?

Back 73

Unpaired RyRs are triggered by the release of Calcium from neighboring coupled RyRs.

Front 74

This is extremely important in Cardiac muscle and less so in skeletal.

Back 74

Calcium induced Calcium release.

Front 75

How is contraction terminated?

Back 75

By removing Calcium from the cytosol.

Front 76

How is calcium pumped out of the cytosol to terminate muscle contraction?

Back 76

Pumped back into SR via Calcium-ATPase. (aka SERCA because its also found in smooth ER)

Front 77

What are the triggereing agents of Malignant Hyperthermia?

Back 77

Succinylcholine or volatile anesthetics such as halothane

Front 78

What are the symptoms of Malignant Hyperthermia?

Back 78

Tachypnea
Low plasma O2, high CO2
Tachycardia
Rigidity
Swings in BP
Muscle Breakdown

Front 79

What is the cause of Malignant Hyperthermia?

Back 79

Basically high intramuscular Calcium release.
Mutation in RyRs causes increased activation/ reduced deactivation so ATP is consumed pumping out the Calcium from the cytosol leading to the generation of heat.

Front 80

Compared to cardiac muscle, the ultrastructure of skeletal muscle is different in what way?

Back 80

The SR is more extensive in skeletal muscle.