Excitation-Contraction Coupling (EC Coupling) PDF

# Excitation Contraction Coupling (EC Coupling) ## Objectives: - What is EC coupling? - The passage of the impulse - The T tubule - Mechanism of Calcium Release - The contraction sequence - Relaxation - Differences in smooth muscles - Differences in cardiac muscles - Applied aspect ## What is EC...

# Excitation Contraction Coupling (EC Coupling) ## Objectives: - What is EC coupling? - The passage of the impulse - The T tubule - Mechanism of Calcium Release - The contraction sequence - Relaxation - Differences in smooth muscles - Differences in cardiac muscles - Applied aspect ## What is EC coupling? - An action potential triggers the contraction of a muscle cell. - Calcium ions can regulate whether or not contraction can occur. - Thus, "the link reaction which is needed to link muscle excitation (the depolarisation of the action potential) to Ca++ release from the sarcoplasmic reticulum is called excitation-contraction coupling". ## Excitation Sequence - The image is a diagram showing the flow of excitation from the excitation sequence to the contraction sequence through a "link" known as EC coupling. ## The Passage of the Impulse - After the conduction of the impulse through the axons to the post-synaptic membrane via the neuromuscular junction, there are conformational changes leading to flux of Na+ ions inside the muscle fibre. - Accumulation of Na+ within the cell commence the depolarisation of the membrane, giving rise to the end plate potential that keeps rising towards an action potential threshold. ## Excitation - The image is of a neuromuscular junction, showing an action potential that is crossing the neuromuscular junction. ## Transfer of Impulse Towards Motor End Plate - The image is the same as the previous image, but it is labelled as "Transfer of impulse towards Motor end plate". ## The Action Potential Spreads Throughout the Fibre and Specially Within the T Tubules - The image shows an enlarged view of a muscle fibre with labelled "T Tubules". - The image shows the action potential travelling down a T Tubule in the muscle fibre. ## The T-tubule - The T tubules are tube-shaped invaginations of the sarcolemma that penetrate throughout the muscle fibre. - The lumen of the T tubule is continuous with the ECF, and the membrane depolarisation during action potential occurs across the T-tubule membrane. - On either side of the T-tubule are swellings of the sarcoplasmic reticulum (SR) called the lateral sacs or terminal cisterns. ## T Tubule Structure - The image is a diagram of a T Tubule structure in a muscle fibre. - It shows that the T Tubule is surrounded by two terminal cisterns of the sarcoplasmic reticulum to form a triad. ## How does depolarisation in the T-tubule membrane open a Ca++ channel in the SR membrane? - Located in the T-tubule membrane, closely associated with the foot of the SR Ca++ Channel, is the T-tubule voltage sensor, better known as, DHPR (dihydropyridine receptor). - The impulse passes to the L tubules containing another receptor - the RyR or Ryanodine receptor. ## The Voltage Sensor, Changes Conformation in Response to the Depolarisation of the Action Potential, and Causes Opening of the - RyR (Ryanodine Receptor - This conformational change is transmitted to the foot of the SR Ca++ Channel causing it to open, and allowing Ca++ release. - Thus, Ca++ ions are released and utilised during contraction of the muscle fibres. ## At Rest and Excitation: T-Tubule Membrane Depolarised - The image shows two diagrams; one of a muscle at rest and one of a muscle with a depolarized T-Tubule membrane. - It shows that in a “resting” muscle, Ca** does not exist in the cytosol. - The image shows that in an “excited” muscle, Ca** is present in the cytosol ## The Contraction Sequence that Follows: - The Ca++ that accumulates, is the reason for initiation and maintenance of the contraction of sarcomere. - The free Ca++ binds with the troponin C protein component of the thin actin filaments introducing the active calcium-troponin complex. ## Binding of Ca++ to the Troponin C - The image shows a zoomed in picture of thick filaments and thin filaments. - It illustrates the binding of Ca** to troponin C. ## There is conformational change in troponin C, which induces alternation in the conformation of the tropomyosin protein - The image shows a zoomed in picture of thick filaments and thin filaments. - It shows the conformational change in troponin C and the alternation in the conformation of the tropomyosin protein. - It also illustrates the exposure of the myosin binding sites of the actin filament using the movement of the tropomyosin. ## Myosin head binds to the sites on the actin filament - The image shows a sarcomere with a labelled A band, I band, Z disk, H zone, myosin myofilament, and actin myofilament. - The release of ADP+iP are tightly coupled to the power stroke, thus resulting in shortening of sarcomere. ## Fully Contracted Muscle - The image shows a fully contracted muscle, with the labelled components from the previous sarcomere image. ## Relaxation - SERCA pump (Sarco- Endoplasmic Reticulum Calcium ATPase pump) is the enzyme responsible for relaxation. - This enzyme pumps calcium back into the sarcoplasmic reticulum from the cytosol. ## Summary - The image of a muscle fibre with a labelled T-tubule, SR, motor end plate, myosin thick filament, and a thin filament, illustrate the whole excitation of a muscle fibre and the contraction sequence. ## Differences in Smooth Muscles: - Calcium channel differences: - Different channels releasing calcium from ECF (RyR still exists though), depends on the type of smooth muscles. - Channels could be voltage-gated, ligand-gated, second messenger-gated or mechanically-gated. - Calcium entrance options: - From gated channels, extracellularly - From IP3 - IP3 (inositol triphosphate) is a second messenger that opens RyR channel which releases calcium from SR. - Calcium binds to calmodulin. - Activation of MLCK (Myosin-light-chain-kinase), causes phosphorylation of the myosin head. ## Differences in Cardiac Muscles: - Cells are coupled as electrical syncytium due to high expression of gap junctions between the cells. - Gap junctions consist of 2 connexons, each made of 6 connexins. - T tubules are very well developed with more diameter. - DIAD is present, ie. With 1-tubule, there is only 1 cistern. ## Applied: - Malignant hyperthermia: - It is due to the mutation in the RyR located in the L-tubules. - Characterised by: - Increased body temperature - Increased muscular contractions and muscle rigidity - Increased heart rate - High fever ## Any Queries? - The image is of a teacher at a blackboard.