Excitation Coupling Flashcards
What is excitation contraction coupling
Linkage between excitation of the muscle fibre membrane and the onset of contraction
role of transverse tubules
- Action potential is propagated from the end plate along the surface of the muscle fibre (sarcolemma)
- Action potential is propagated into the fibre down the T-tubule membrane
- Depolarisation of the T-tubule membrane is ‘signalled’ to the membrane of the terminal cisternae
what two compartments is calcium recycled between
– Sarcoplasmic reticulum/terminal cisternae – Cytoplasm
what are the two types of junctional foot proteins
– Dihydropyridine receptor protein (DHPR)
• L-type voltage-gated calcium channel in the T- tubule membrane
– Ryanodine receptor protein (RYR)
• Calcium release channel in the SR
Dihydropyridines blocking drugs
Nifedipine
what is Nifedipine used to treat
Used to treat (smooth muscle)
– Hypertension
– Migraine
– Atherosclerosis
Ryanodine muscle relaxant
– Dantrolene
what is Dantrolene used to treat
– Muscle spasm
• Malignant hyperthermia
what is malignant hypothermia
- Severe reaction to commonly used anaesthetics and depolarising muscle relaxants
- First manifestations of MH occur in the operating room
- Fatal if untreated
what are symptoms of malignant hypothermia
Symptoms • Muscle rigidity • High Fever • Increased acid levels in blood and other tissues • Rapid heart rate
what is the underlying cause of malignant hypothermia
• Point mutations in the gene coding for RyR1
what is SERCA
SERCA – Sarcoplasmic Endoplasmic Reticulum Calcium ATPase
What activates SERCA
The increase in intracellular calcium concentration activates a Ca2+ ATPase (calcium pump) in the SR membrane
What is the role of SERCA
Active transport of calcium from the cytoplasm into the SR (2 Ca2+ ions per molecule ATP hydrolysed)
• [Ca2+]decreasesto<10-7M-RELAXATION
Role of calsequestrin
Stores calcium at high concentrations in the terminal cisternae to establish a concentration gradient from the SR to the cytoplasm
Pacemaker cells
- Specialised muscle cells
- Unstable resting potential
- Undergo automatic rhythmical depolarisation
parasympathetic neurotransmitter action and innveration
acetyl choline
slows rate
localised to pacemakers
Sympathetic neurotransmitter, action, innervation
nor-adrenaline, increases rate and strength, diffuse
What happens on the release of calcium
The increase in intracellular calcium concentration from < 10-7 M to > 10-5 M is the KEY event which ultimately leads to force generation through the interaction of actin and myosin filaments
what percentage of calcium enters through the DHPR L-type calcium channel to induce CICR
25%
what percentage of calcium enters through the calcium sensitive calcium release RYR protein in the SR
75%
Relaxation in cardiac muscle
• Requires a decrease in cytoplasmic Ca2+ concentration from
>10-5 M to < 10-7 M
• Ca2+ ATPase in sarcoplasmic reticulum is activated
• Ca2+ ATPase in the cell membrane pumps out the trigger Ca2+
• Na+:Ca2+ exchange in the sarcolemmal membrane (3:1)
what is the role of the sodium calcium exchanger
helps pump calcium outside of the cell, key cause of arythmias as if too much sodium is being pumped in there is an AP triggered when there shouldn’t be
