Excitation-Contraction Coupling In Cardiac Muslce Flashcards
A brief pulse of calcium causes what?
An intracellular signal
Prolonged elevation of calcium causes what?
Cytotoxicity
Good use of calcium
Fertilisation (flask block of egg to prevent another sperm entering) Proliferation Secretion Heart beat Muscle contraction
Bad causes of calcium
Apoptosis Ischemia / reperfusion Excitotoxicity Cardiac arrhythmia Malignant hyperthermia
Electrical activity of the heart
SA node AV node Bundle of His Bundle Branches Purkinje Fibres
Describe the p wave
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
Describe Q wave
Downward wave = septal depolarisation. Very wide and deep after a heart attack
Describe and R wave
Upwards deflection. Early ventricular depolarisation
Describe S wave
Negative deflection. Late ventricular depolarisation
Describe T wave
Up right, rounded, slightly asymmetrical = repolarisation of ventricles
What is the relationship between Ca2+ permeability and contraction force?
As Ca2+ permeability increases the relative force increases, however, their is a ceiling as to how strong the force is and will plateau
Calcium concentration in the cytoplasm is mediated by?
Ryanodine receptors (RyRs) Plasma membrane calcium L-type channels (LTCC) SERCA - SR calcium pump (calcium-ATPase) Na/Ca exchangers (NCX)
L-type voltage gated calcium channels (dihydropyridine receptors; DHPRs)
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
Ryanodine receptors (RyRy) function and how they work?
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
Na/Ca Exchanger (NCX) function and how do they work?
A plasma membrane enzyme that exchanges 3 moles of Na for 1 mole of Ca either inward or outward- depending on the ionic gradient.
Sarcoplasmic reticulum (SR) function and how do they work?
An organelle membrane system that encases each myofibril within a muscle cell.
Essential component of SR is the calcium pump.
Sarco(endo)plasmic reticulum Ca-ATPase (SERCA) pump function and how do they work?
SERCA resides in the SR plasma membrane.
Couples to ATP hydrolysis to transport of calcium from cytosolic luminal space.
what does Phospholamban (PLB) do?
Receives phosphates. It is the major phosphoprotein component of the sarcoplasmic reticulum. This helps to regulate cardiac sarcoplasmic reticulum calcium uptake.
Definition of phosphorylation
Turns many protein enzymes on and off, thereby altering their function and activity.
PLB can be phosphorylated at 3 distinct sites by various protein kinases, where are these points?
Serine 10 = protein kinase C
Serine 16 = protein kinase A and Protein Kinase G
Threonine 17 = Calcium - calmodulin - dependent protein kinase,
What is the role of PLB in regulating cardiac function
Dephosphorylation form - PLB is an inhibitor of SERCA.
Phosphorylated form - PLB dissociates from SERCA, thus activating the pump.
Summarise myocyte contraction
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.
Describe the cardiac contractile protein and the contraction cycle.
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.
What mechanism influences cytosolic calcium concentrations?
beta-adrenoreceptor - coupled mechanism
What regulates the heart rate?
Autonomic nervous system
What are chronotropic agents?
Factors influencing the currents alter the slope of the pacemaker and therefore the heart rate.
How does cardiac signal transduction mechanism alter excitation-contraction coupling?
Sympathetic stimulation increases cardiac muscle contractility.
What is the beta-adrenergic receptor signalling pathway?
Noradrenaline/ adrenaline beta 1 - adrenergic receptor Activates GTP-binding protein (Gs) Stimulates adenylyl cyclase (AC) cAMP PKA Phosphorylates several proteins related to EC-coupling.
Describe ionotropic modulation of calcium by sympathetic pathway
Increases developed contraction (e.g. affecting the force of cardiac contraction)
Describe lusitropic modulation of calcium by sympathetic pathway
Affecting cardiac relaxation
Lusitropic effect of PKA is mediated how?
Via phosphorylation of PLB and troponin I. This mechanism speeds up calcium re-upake and dissociation of calcium from the myofilaments.
Ionotropic effect of PKA is mediated how?
The combination of increased intracellular calcium and greater availability of SR calcium.
What are RyRs phosphorylated by?
PKA
