L: excitation contraction coupling in cardiac and skeletal muscle

complete

What is excitation contraction coupling?

Linkage between excitation of the muscle fibre membrane and the onset of contraction.

What length is the skeletal muscle action potential?

Very short action potential.

What does depolarisation cause for the membrane potential?

It causes it to become more positive

What is the latent period?

The time between stimulation and the onset of contraction

What can be said about the action potential and the tension of skeletal muscle?

They don’t overlap

What are changes in the electric field restricted to in the latent period?

The immediate vicinity of the plasma membrane.

Are excitation and contraction coupled in the latent period?

Yes, but contraction hasn’t started yet.

What does calcium bind to?

Troponin

What is the terminal cisterna?

A specialised structure in the sarcoplasmic reticulum

Which receptor senses a change in the membrane potential?

DHP - dihydropyradine receptor

What receptor does dihydropyridine signal to and where is it located?

Ryanodine type 1 - sarcoplasmic reticulum

What does the depolarisation of the T tubule do to DHP?

Causes a conformational change which allows some calcium to flow through

Where is the action potential propagated from?

from the end plate - along the surface of the sarcolemma

The depolarisation of the T-tubule is “signalled” to the membrane of what structure?

Terminal cisternae

Where does the calcium come from in skeletal muscle?

It is recycled between 2 intracellular compartments

Which two compartments are calcium ions recycled between in skeletal muscle?

• the sarcoplasmic reticulum/terminal cisternae

• the cytoplasm

What is a key difference between the activation of skeletal and cardiac muscle?

There is no requirement for extracellular Ca2+ in skeletal muscle during the activation of contraction.

What type of membrane protein is dihydropyridine receptor protein (DHPR/DHP)?

L-type voltage-gated calcium channel (in the t-tubule membrane)

What type of membrane protein is ryanodine receptor protein (RYR)?

Calcium release channel

Where can you find ryanodine receptor protein (RYR)?

In the sarcoplasmic reticulum

What is the junctional foot protein?

A mechanical linkage of DHPR of the T-tubule and RYR of the sarcoplasmic reticulum.

What causes the DHP receptor to open?

Membrane depolarisation/action potential

What causes the RYR protein to open?

The DHP receptor protein letting calcium into the cell

When the calcium ions exit through the RYR and into the cytoplasm, are they travelling down or up a concentration gradient?

The are diffusing down a steep concentration gradient

What happens to the cytoplasmic calcium concentration after calcium is released?

<10^-7 M to >10^-5M

What is the key event that leads to force generation throughout the interaction of actin and myosin?

The increase in intracellular calcium concentration

What does SERCA stand for?

Sarcoplasmic Endoplasmic Reticulum Calcium ATPase

What is SERCA activated by?

An increase in intracellular calcium

Where can you find SERCA?

In the sarcoplasmic reticulum membrane

Is the transport of calcium back into the sarcoplasmic reticulum in skeletal muscle active or passive transport?

Active transport

How many calcium ions are transported into the SR for each ATP molecule hydrolysed?

2 Ca²⁺ ions

What does the cytoplasmic calcium concentration decrease to when the cell relaxes?

<10^-7M

What is the role of calsequestrin in skeletal muscle?

It stores calcium at high concentrations in the terminal cistern to establish a concentration gradient from the SR to the cytoplasm

What is the name of the calcium binding protein in the terminal cisternae?

calsequestrin

What is the molecular weight of calsequestrin?

44000

How many calcium ions does calsequestrin bind per molecule?

43

What does calsequestrin do to the concentration gradient?

It decreases the concentration gradient as it mops up the free calcium

What causes malignant hyperthermia?

A mutation in ryanodine type 1 receptor

What does malignant hyperthermia mean for the ryanodine receptor?

It is locked in the open state meaning there is an influx of calcium ions, muscles contract and more ATP is used leading to increased temperature. There can also be breakdown of muscle tissue

What type of disorder is malignant hyperthermia?

A pharmacogenetic disorder of skeletal muscle

What is malignant hyperthermia a severe reaction to?

Commonly used anaesthetics and depolarising muscle relaxants

Where do the first manifestations of malignant hyperthermia occur?

In the operating room

What happens if malignant hyperthermia is left untreated?

• Lactic acidosis

• Hyperkalaemia

It can also be fatal

What are the symptoms of malignant hyperthermia?

• muscle rigidity

• tachypnoea

• tachycardia

• hyperthermia - can rise as rapidly as 1 degree every five minutes

• increased CO2 production

What type of mutation is responsible for the change in the RYR1 protein?

Point mutations

What is the treatment for malignant hyperthermia?

• Intravenous administration of the drug Dantrolene

• Cessation of anaesthesia

• aggressive efforts to cool the body

What are pacemaker cells?

Specialised muscle cells in cardiac muscle that can spontaneously generate electrical impulses

What can be said about the resting membrane potential of pacemaker cells?

It is unstable

what do pacemaker cells always depolarise to?

Threshold

What do pacemaker cells undergo?

automatic rhythmic depolarisation

Where does the sinoatrial node affect directly?

The right and left atrium

What does the atrioventricular node affect directly?

The right and left ventricle.

What parasympathetic neurotransmitter exists in cardiac muscle and what is its function?

Acetyl choline and it slows the heart rate

What is a sympathetic neurotransmitter in cardiac muscle and what is its function?

Nor-adrenaline and it increases the rate and strength of contraction

Where is the parasympathetic innervation of cardiac muscle localised to?

Pacemakers

By what mechanism does nor-adrenaline affect cardiac muscle?

diffusing

Which has a longer action potential - skeletal or cardiac muscle?

Cardiac muscle

What can be said about the action potential and the tension of cardiac muscle?

They overlap (contraction occurs during the action potential)

What is Ca2+ induced Ca2+ release (CICR)?

25% of the required Ca2+ enters through the DHP receptor in the T tubule membrane which triggers the release of Ca2+ via the Ca2+ sensitive ryanodine channels in the SR

What does T tubule stand for?

transverse tubule

Is there a requirement for extracellular calcium in cardiac muscle?

yes

What are the percentages of the origins of calcium in cardiac muscle?

• 25% from the DHPR (L-type calcium channel)

• 75% through the calcium sensitive calcium release RYR protein in the SR

What does relaxation of cardiac muscle require of the cytoplasmic Ca2+ concentration?

A decrease from >10^-5M to <10^-7M

What happens to the Ca2+ATPase in the SR when cardiac muscle relaxes?

It is activated and takes calcium back into the SR

What happens to the Ca2+ATPase in the cell membrane when cardiac muscle relaxes?

It pumps out the trigger Ca2+

What is the sodium to calcium ratio of exchange in the sarcolemmal membrane during relaxation of cardiac muscle?

3:1

What is a ryanodine receptor type 2 channelopathy?

Catecholaminergic polymorphic ventricular tachycardia (CVPT)

How do you get CPVT?

It is an inheritable autosomal dominant condition

How is the arrhythmia displayed by CPVT patients characterised?

Ventricular tachycardia that occurs with stress or exercise

What are symptoms of catecholaminergic polymorphic ventricular tachycardia?

• Sudden dizzy spells

• fainting episodes

• sudden cardiac death

How many point mutations were identified in the RyR2 gene when patients were screened for CPVT1?

69 point mutations