Flashcards in *Pharmacology 1 (lecture 1) Deck (59)
What causes phase 4 of the action potential in nodal tissue of the heart?
Increased Na+ influx
Decreased K+ efflux
What causes phase 0 of the action potential in nodal tissue of the heart?
Increased Ca2+ influx
What causes phase 3 of the action potential in nodal tissue?
Increased K+ efflux
What transmits Na and K movement during phase 4?
What switches this on? (nodal tissue)
The funny current - Hyperpolarisation-activated and cyclic nucleotide gated channels (HCN channels)
Hyperpolarisaiton (Very negative)
What causes stage 3 of the action potential in nodal tissue?
Repolarisation caused by K+ efflux (delated rectifier potassium channel)
What causes phase 0 of the action potential in cardiac myocytes?
Fast Na+ influx
What causes phase 1 of the action potential in cardiac myocytes?
Transient K+ efflux
What causes phase 2 of the action potential in cardiac myocytes?
Ca2+ influx, also a small bit of Na+ influx and NCX1 operating in reverse direction (Normally brings 3 Na in and expels 1 Ca but now brings 1 Ca in and pumps 3 Na out)
What causes phase 3 of the action potential in cardiac myocytes?
What is the difference between noradrenaline and adrenaline?
Noradrenaline is a post-ganglionic neurotransmitter where as adrenaline is a hormone
In terms of the sympathetic system on the heart, what receptor is stimulated and where are these located?
What protein does B1 adrenoceptors use and what enzyme is activated?
What does adenylyl cyclase do? (B1 adrenoceptor)
Converts ATP to cAMP
What does activation of B1 adrenoceptors cause? (8)
Increased heart rate
Increased conduction velocity in AV node
Decreased duration of systole
Decrease in cardiac efficiency
Increased activity of the Na+/K+/ATPase
Increased mass of cardiac muscle
What causes an increased heart rate due to sympathetic stimulation? (2)
Mediated by the SA node and due to an increase in the slope of phase 4 depolarisation (caused by enhanced If and Ica) and reduction in the threshold for AP initiation caused by enhanced Ica
What causes the positive inotropic effect due to sympathetic stimulation?
Increase in phase 2 of the cardiac action potential in atrial ad ventricular mycoses and enhanced Ca2+ influx and sensitisation of contractile proteins to Ca2+
What cause an increased conduction velocity in the heart?
Enhancement of If and Ica
Why is increased activity of the Na+/K+ATPase important in sympathetic stimulation of the heart?
For depolarisation and restoration of function following generalised myocardial depolarisaiton
What happens to the stroke volume due to sympathetic stimulation?
It increases along with contractility (Frank-starling curve)
What receptor does the parasympathetic system controlling the heart stimulate?
What effect does this have on what enzyme?
What other effect does it have?
M2 muscarinic cholinoceptors mainly in nodal cells
Decreases activity of adenylyl cyclase
Opens potassium channels (GIRK) to cause hyper-polarisation of SA node (mediated by Gi B gamma subunits)
What effects does parasympathetic stimulation have on the heart? (3)
Decreased heart rate
Decreased conduction in AV node
What 3 factors cause the decreased heart rate due to parasympathetic stimulation?
Decreased slope of pacemaker potential due to a reduction in the funny current
Opening of GIRK = hyper polarisation
Increase in threshold for AP due to reduced ICa2+
Where does decreased contractility due to para. stimulation effect?
What causes decrease contractility due to para. stimulation?
Decrease in phase 2 of action potential and decrease in Ca2+ entry
How can parasympathetic stimulation predispose to arrhythmias?
Predisposes to arrhythmias in the artier as AP duration is reduced ad correspondingly the refractory period (predisposes to re-enterant arrhythmias)
What can vagal manoeuvres be attempted to treat?
Atrial tachycardia - increases parasympathetic output therefore suppressing impulse conduction through the AV node
2 typesof vagal manouvres and what they do?
Valsalva manoeuvre - activate aortic baroreceptors by breathing techniques
Massage of bifurcation of the carotid artery to stimulate baroreceptors in the carotid sinus
What activates HCN channels (the funny current)?
How does Ivabradine work?
What is it used to treat?
It is a selective blocker of HCN channels meaning it slows heart rate by decreasing the slope of the pacemaker potential
Angina - by slowing the heart, O2 consumption is reduced