Lecture 4.2 - Initiation and Control of Electrical Activity in the Heart PDF

Cardiomyocytes: ◦Elongated, cylindrical, striated cells ◦Have single nucleus ◦Contain high numbers of mitochondria - as these cells are contracting multiple cells ◦Gap junctions: Allow the depolarising current to flow through the cardiac muscle cells from one to another...

Cardiomyocytes: ◦Elongated, cylindrical, striated cells ◦Have single nucleus ◦Contain high numbers of mitochondria - as these cells are contracting multiple cells ◦Gap junctions: Allow the depolarising current to flow through the cardiac muscle cells from one to another ‣ Nodal cells generate the action potential MASS ◦Desmosomes - serve to anchor ends of cardiac muscle fibres together ‣ Allows efficiency between cells man ◦Gap junctions and desmosomes collectively form intercalated discs ◦Histology - specialised cell junctions (intercalated discs - ID) ‣ Holds the different cardiomyocytes together Automaticity of the heart: ◦Intrinsic ability to generate action potentials spontaneously and depolarise contractile myocardial cells, causing them to contract ‣ Brain doesn't control initiation of the action potential - APs are generated spontaneously by the nodal cells Nodal cells: ◦SA node: ‣ Located just beneath superior vena cava ‣ Pacemaker of the heart ‣ Can generate action potentials and are non-contractile Transfer AP to contractile cells ‣ These cells set the sinus rhythm, which is automatic: 60-80 bpm ‣ Set without any extrinsic innervation ◦AP is generated and then passes through the internodal pathway ◦Bachmanns' bundle - pass signals from SA node to left atrium ‣ Therefore the left atrium now contracts ◦AV node: ‣ Located just beneath the pulmonary trunk ‣ Act as connection between atria and ventricles  ‣ 0.1s delay in conduction in AV node - Purpose: Gives adequate time for atria to contract before ventricles mm ◦AV bundle (Bundle of His) - carries action potentials from AV node to bundle branches ◦Right bundle branch (RBB) - carries action potentials to right myocardium ◦Left bundle branch (LBB) - carries action potentials to left myocardium ◦Purkinje fibres - carries action potentials to ventricular muscle Slow response action potentials - nodal cells: ◦Resting membrane potential (RMP) of nodal cells = -60mV ◦SA nodal cells have an unstable RMP that spontaneously depolarises due to pacemaker me potential the ◦Phase 4: Diastole- funny Na+ channels open: -60mV -> -55mV 88 ‣ T-type Ca2+ channels open: -55mV -> -40mV ◦Threshold potential reached (-40mV) ◦Phase 0 (upstroke): L-type Ca2+ channels open: -40mV -> +10mV stood ◦Phase 3 (final repolarisation): ‣ L-type Ca2+ channels inactivate at +10mV ‣ K+ channels activate and K+ starts exiting the cell, so inside of cell becomes more negative ‣ Cell repolarisation ◦At -60mV, K+ channels close and funny Na+ channels open and phase 4 begins Fast response action potentials: contractile cells: ◦RMP of contractile cells: -90mV ◦Positive ions from modal cells move into contractile cells via gap junction ◦In-flow of positive ions: -90mV -> -70mV (threshold) ◦Phase 0 (upstroke): voltage-gated Na+ channels open: -70mV -> +20mV ‣ In-flow of Na+ cells in contractile cells is much faster than the Ca2+ cells in nodal cells, hence why the graph becomes very steep in phase 2) - this explains why it is called fast response AP ‣ Contractile cells are depolarised at this point ◦When +20mV is reached, Na+channels close ◦Phase 1 (initial repolarisation): K+ channels open and K+ moves out and brings the membrane potential to 0mV ‣ Membrane potential decreases ◦Phase 2 (plateau): K+ moved out and Ca2+ moves in (L-type channels are activated) ‣ Membrane potential doesn't change in phase 2 because there is an equal number of positive ions moving in and out of the cell simultaneously (membrane potential doesn't change on the graph in phase 2) Excitation-contraction coupling: ◦Occurs in phase 2 ◦Ca2+ ions activate ryanodine receptors (RyRs) in sarcoplasmic reticulum ◦RyR opens up channels and more Ca2+ ions move out into the cytoplasm  ◦Ca2+ ions bind to troponin -> changes the shape of tropomyosin -> moves tropomyosin away -> allowing myosin head to interact with actin -> more cross-bridges formed -> more contraction -> more pumping of blood ◦Multiple cardiomyocytes receive signals at same time, synchronise their action, they contract together as a unit -> functional syncytium. Fast response action potentials: contractile cells: ◦Phase 3 (final repolarisation): L-type Ca2+ channels close ‣ Membrane potential decreases fast ◦Ca2+ is taken back to sarcoplasmic reticulum or outside the cell via Sodium-calcium exchanger and calcium proton ATPase pumps ◦Ca2+ is taken back to ECF via sodium-calcium exchanger and calcium proton ATPase pumps ◦K+ channels opens and K+ starts exiting the cell ◦Phase 4 (resting membrane potential) - very little movement of ions ‣ Graph plateaus at this point Action potentials - nodal vs contractile cells: Refractory period and changes in action potential: ◦The membrane potential determines whether voltage-gated channels open or close. ◦In contractile cells, excitability depends on the availability of voltage-dependent Na+ channels ◦Once a fast-response action potential has been initiated, the depolarised cell cannot be re-excited until it has repolarised because there are not enough Na+ ions (if it is in phase 1 or 2)- refractory period ‣ It is only when you reach phase 3 that the Na+ channels are reactivated and the next AP can take place ◦If an excitation occurs prematurely the resulting action potential will be of smaller amplitude -> lower contraction ◦In nodal cells, excitability depends on the availability of L-type Ca2+ channels (which are responsible for phase 0) ◦In nodal cell, the refractory period frequently extends well beyond phase 3 (it is longer in comparison to contractile cells) ◦If an excitation occurs prematurely the resulting action potential will be of smaller amplitude