Cardiac contraction

Pregunta	Respuesta
1. An ______ _________ arrives at the __ __ node and causes _____________	action potential, AV, depolarisation
2. There is an influx of ____ ions, which causes ______ ________ ______ ______ to open slowly in the ___ _______ of cardiac myocyte membranes. This is called the _______ ________	Na+, voltage gated calcium channels, T tubules, plateau phase
3. Underneath the __ ______ is the _________ _________. Ca++ binds to _________ _________ on its surface and causes ______ __________ ________ _________.	T tubules, sarcoplasmic reticulum, Ryanodine receptors, Calcium-induced calcium release
4. ___ ions bind to ________ on cardiac muscle fibres, exposing the _______ binding site and allowing _______ ______ to form and contraction to occur.	Ca++, troponin, myosin, cross bridges
At rest, myocytes do not fully ______, so that if needed, a higher influx of ___ will give stronger _________.	contract, Ca++, contraction
Once the myocyte is _______, there is no more ___ influx and the __ __ __ __ are closed.	repolarised, Ca++, VDCCs
During _________ _________: 1. __ __ __ __ from sarcoplasmic reticulum stops 2. __ ions leave the cell by __/__ exchanger 3. __ ions leave the cell via an ______ pump 4. _______ pumps __ back into sarcoplasmic reticulum 5. ___ ions enter mitochondria	isovolumetric relaxation, CICR, Ca++, Ca++/Na+ Ca++, ATPase, Ca++ ATPase, Ca++, Ca++
There is no longer any __ ions available for _______ so _______ occurs	Ca++, contraction, relaxation
What are positive inotropes?	Substances that increase the strength of contraction
When might drugs be given which are positive inotropes?	To increase contractility in heart failure patients
Name 2 classes of positive inotropes?	1. Sympathomimetics 2. Cardiac glycosides
Name 2 sympathomimetics	1. Dobutamine 2. Dopamine
What do they do?	Stimulate beta 1 receptors
How does that increase contractility?	beta 1 receptors are linked to the Gs pathway which causes increased cAMP and PKA. PKA phosphorylates VDCCs so their activity increases = more Ca++ influx and higher contractility
Despite quicker APs, the time for _______ remains similar so __ __ is maintained. However if HR is excessively increased, ________ will be too short to sustain __ __.	diastole, SV, diastole, SV
What does amrinone do?	Inhibits phosphodiesterase so cAMP is not broken down. Only used in severe cases.
Name a cardiac glycoside	Digoxin (from the foxglove)
How do they work?	Stop Ca++ from being extruded from cells.
How do they do this?	Inhibit Na+/ K+ pump so intracellular Na+ builds up. This prevents the Na+/Ca++ exchanger from working (maybe even reversing it). More Ca++ is also stored in the SR for more CICR next time.
What else can digoxin be used for?	Atrial fibrillation - increases activity of vagus nerve = increased ACh = slower HR
What is the disadvantage?	Can have toxic side effects - LOW therapeutic index

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