Excitation-Contraction Coupling In Cardiac Muslce

Question 1

A brief pulse of calcium causes what?

Answer 1

An intracellular signal

Question 2

Prolonged elevation of calcium causes what?

Answer 2

Cytotoxicity

Question 3

Good use of calcium

Answer 3

Fertilisation (flask block of egg to prevent another sperm entering)
Proliferation
Secretion
Heart beat
Muscle contraction

Question 4

Bad causes of calcium

Answer 4

Apoptosis 
Ischemia / reperfusion 
Excitotoxicity
Cardiac arrhythmia 
Malignant hyperthermia

Question 5

Electrical activity of the heart

Answer 5

SA node 
AV node
Bundle of His
Bundle Branches 
Purkinje Fibres

Question 6

Describe the p wave

Answer 6

Small, upwards wave = atrial depolarisation.
Initial portion of the p wave is right atrial depolarisation the terminal portion is left atrial depolarisation and lasts around 0.3mV

Question 7

Describe Q wave

Answer 7

Downward wave = septal depolarisation. Very wide and deep after a heart attack

Question 8

Describe and R wave

Answer 8

Upwards deflection. Early ventricular depolarisation

Question 9

Describe S wave

Answer 9

Negative deflection. Late ventricular depolarisation

Question 10

Describe T wave

Answer 10

Up right, rounded, slightly asymmetrical = repolarisation of ventricles

Question 11

What is the relationship between Ca2+ permeability and contraction force?

Answer 11

As Ca2+ permeability increases the relative force increases, however, their is a ceiling as to how strong the force is and will plateau

Question 12

Calcium concentration in the cytoplasm is mediated by?

Answer 12

Ryanodine receptors (RyRs)
Plasma membrane calcium L-type channels (LTCC)
SERCA - SR calcium pump (calcium-ATPase)
Na/Ca exchangers (NCX)

Question 13

L-type voltage gated calcium channels (dihydropyridine receptors; DHPRs)

Answer 13

Slow, or L-type voltage gated calcium channel. Located on the plasma membrane
Requires membrane potential greater than -30mV for activation.
Essential for initiation and regulation of EC coupling
When smooth muscle depolarises, it causes the L-type channels to open
Found in close junction of the SR and rapid influx of calcium though L-type channels causes release of intracellular calcium from SR stores

Question 14

Ryanodine receptors (RyRy) function and how they work?

Answer 14

Mediate the release of calcium ions from the SR
Plays an essential role in muscle contraction
Regulated by protein-protein interactions with the L-type channel
RyRy channels interact with the L-type channels in the nearby tubule membrane - this is known as EC coupling
Depolarisation of the t-tubule membrane induces conformational changes in L-type channel which ultimately lead to activation of RyR channel in the SR membrane

Question 15

Na/Ca Exchanger (NCX) function and how do they work?

Answer 15

A plasma membrane enzyme that exchanges 3 moles of Na for 1 mole of Ca either inward or outward- depending on the ionic gradient.

Question 16

Sarcoplasmic reticulum (SR) function and how do they work?

Answer 16

An organelle membrane system that encases each myofibril within a muscle cell.
Essential component of SR is the calcium pump.

Question 17

Sarco(endo)plasmic reticulum Ca-ATPase (SERCA) pump function and how do they work?

Answer 17

SERCA resides in the SR plasma membrane.

Couples to ATP hydrolysis to transport of calcium from cytosolic luminal space.

Question 18

what does Phospholamban (PLB) do?

Answer 18

Receives phosphates. It is the major phosphoprotein component of the sarcoplasmic reticulum. This helps to regulate cardiac sarcoplasmic reticulum calcium uptake.

Question 19

Definition of phosphorylation

Answer 19

Turns many protein enzymes on and off, thereby altering their function and activity.

Question 20

PLB can be phosphorylated at 3 distinct sites by various protein kinases, where are these points?

Answer 20

Serine 10 = protein kinase C
Serine 16 = protein kinase A and Protein Kinase G
Threonine 17 = Calcium - calmodulin - dependent protein kinase,

Question 21

What is the role of PLB in regulating cardiac function

Answer 21

Dephosphorylation form - PLB is an inhibitor of SERCA.

Phosphorylated form - PLB dissociates from SERCA, thus activating the pump.

Question 22

Summarise myocyte contraction

Answer 22

Increased cytosolic Ca2+ during ventricular action potential through L-type Ca2+ channels in the sarcolemma. This stimulates the RyR in the SR membrane, causing release of stored Ca2+ from the SR into the cytosol. When the Ca2+ concentration = 10-5M, calcium binds to troponin C (TN-C)and induces a conformational change in tropomyosin that releases the inhibitory protein troponin this causes an interaction site for myosin on the actin filament, and the binding of myosin to actin initiates the contraction cycle.

Question 23

Describe the cardiac contractile protein and the contraction cycle.

Answer 23

Hydrolysis of ATP to ADP by myosin. Ca2+ is released from the SR and binds to TN-C, causing a conformational change into tropomyosin that allows myosin to form an active complex with actin. Dissociation of ADP from myosin allows the myosin head to bend: this pulls the Z lines closer together and shortens the bands = contraction state (referred to as rigor complex). Binding of a new ATP molecule to myosin allows the actin-myosin complex to dissociate, Ca2+ also dissociates from the TN-C and the contraction cycle is repeated.

Question 24

What mechanism influences cytosolic calcium concentrations?

Answer 24

beta-adrenoreceptor - coupled mechanism

Question 25

What regulates the heart rate?

Answer 25

Autonomic nervous system

Question 26

What are chronotropic agents?

Answer 26

Factors influencing the currents alter the slope of the pacemaker and therefore the heart rate.

Question 27

How does cardiac signal transduction mechanism alter excitation-contraction coupling?

Answer 27

Sympathetic stimulation increases cardiac muscle contractility.

Question 28

What is the beta-adrenergic receptor signalling pathway?

Answer 28

Noradrenaline/ adrenaline
beta 1 - adrenergic receptor
Activates GTP-binding protein (Gs)
Stimulates adenylyl cyclase (AC)
cAMP
PKA 
Phosphorylates several proteins related to EC-coupling.

Question 29

Describe ionotropic modulation of calcium by sympathetic pathway

Answer 29

Increases developed contraction (e.g. affecting the force of cardiac contraction)

Question 30

Describe lusitropic modulation of calcium by sympathetic pathway

Answer 30

Affecting cardiac relaxation

Question 31

Lusitropic effect of PKA is mediated how?

Answer 31

Via phosphorylation of PLB and troponin I. This mechanism speeds up calcium re-upake and dissociation of calcium from the myofilaments.

Question 32

Ionotropic effect of PKA is mediated how?

Answer 32

The combination of increased intracellular calcium and greater availability of SR calcium.

Question 33

What are RyRs phosphorylated by?

Answer 33

PKA