Flashcards in CVS Session 4 Deck (106):
What is the main factor causing establishment of the resting membrane potential?
Potassium permeability of the CSM at rest
Which channels in the CSM are open at rest?
Inward rectifier potassium channels
Why is the resting membrane potential of a cardiac myocyte -90 mV and not Ek (-95 mV)?
Small permeability of CSM to other ions
Between which two equilibrium potentials does the membrane potential of a ventricular myocyte stay within throughout an action potential?
Sodium (+30 mV)
Potassium (-90 mV)
How long does a ventricular action potential last?
What determines the point of plateau in a ventricular action potential?
What causes the upstroke of a ventricular action potential?
Opening of V-G sodium channels --> sodium influx
What two events cause the initial repolarisation of the ventricular action potential?
Transient V-G outward potassium channels --> potassium efflux
Reversal of NCX caused by depolarisation --> small -ve current
What causes the plateau of action potential in a ventricular cardiac myocyte?
Opening of V-G L-type calcium channels --> calcium influx balanced w/ potassium efflux
What causes repolarisation of the ventricular action potential?
V-G potassium channels --> potassium efflux
How do V-G potassium channels vary?
Depend on myocyte present - different types behave differently contributing differently to electrical properties of the myocyte
How is the membrane potential of SAN cells described?
What is the pacemaker potential?
Slow depolarisation to threshold
What initiates Ip?
Membrane potential more -ve than -50 mV activating hyperpolarisation-activated cyclic-nucleotide (HCN) gated channels
What do HCN channels do?
Allow sodium influx at SAN myocyte membrane potential
Also potassium influx at other potentials
How can the activation of the pacemaker potential be increased?
A more -ve membrane potential
After threshold has been reached, what causes the upstroke of the SAN action potential?
Opening of V-G calcium channels --> calcium influx
What causes the downstroke of the SAN action potential?
Opening of V-G potassium channels --> potassium efflux
Why do pacemaker cells not require innervation?
They do not sit at rest so have natural automaticity
Why is the SAN the 'master pacemaker'?
It is fastest to depolarise so sets rhythm of contraction
What will take over the pacemaker function of the SAN if it is compromised?
How are the action potential graphs of the SAN and AVN related?
Similar shape but AVN is over a longer period of time
How are the action potential graphs of atrial muscle, Purkinje fibre and ventricular muscle cells related?
All similar shape w/ resting potential around -80 mV
What is the approximate resting membrane potential of the pacemaker cells?
What gives cardiac muscle cells mechanical strength?
Glycoprotein that spans membrane and crosses gap b/w cells - desmosome
What facilitates electrical coupling of cardiac cells?
Connexon subunits on both sides of membrane forming non-specific pore - gap junction
What is the function of intercalated disks?
To join cardiac muscle cells
Describe the nucleus in a cardiac muscle cell.
What releases 25% of the calcium needed for the sliding filament model in cardiac muscle cells?
Depolarisation opening L-type calcium channels in T-tubules
What causes calcium-induced calcium release?
Localised increase in calcium concentration opens CICR channels in sarcoplasmic reticulum
Why is there a close link b/w L-type calcium channels and CICR channels in cardiac muscle cells?
Cardiac tissue needs actual calcium influx for contraction
What function does calcium perform during contraction of the cardiac muscle cell?
Binds to TnC --> conformational tropomyosin change --> reveals myosin binding site on actin
What function does calcium have during diastole?
Increased calcium concentration stimulates SERCA --> calcium moves into SR --> sarcolemmal calcium ATPase and sodium/calcium exchanger pump calcium out of the cell through the CSM
How is the tone of BV controlled?
Smooth muscle cells in tunica media of arteries, arterioles and veins
How do the actin filaments in myocytes of BV compare to those in other cells?
Longer so can shorten cell more
How are actin filaments in BV myocytes anchored within the cell?
What can cause excitation-contraction coupling of BV myocytes?
Activation of GPCRs
How does depolarisation cause excitation-contraction coupling?
Allows entry of calcium through calcium channels
What class of GPCRs are activated in excitation-contraction coupling?
Give a brief overview of the activation of GPCRs causing excitation-contraction coupling.
IP3 acts as calcium channel --> SR releases calcium --> calcium binds to calmodulin instead of TnC --> MLCK activated which phosphorylates regulatory light chain on myosin head --> actin-myosin interaction
What affect does decreasing calcium levels have on myosin light chain phosphatase?
Causes it to dephosphorylate the myosin light chain --> no interaction --> relaxation
What is PKA?
Protein Kinase A - phosphorylates MLCK therefore inhibiting contraction as it prevents it phosphorylating the light chain on myosin head
What is PKA regulated by?
Why does the contraction of a BV myocyte last longer than in other myocytes?
Attachment formed during contraction can become locked
What does the ANS exert control over?
Vascular and visceral smooth muscle
Rate and force of contraction of the heart
What are enteric neurones usually controlled by?
Sympathetic and parasympathetic nerve fibres
Where do parasympathetic neurones synapse?
In ganglia close to target tissue
How do the lengths of the pre- and post-ganglionic nerve fibres compare?
Which neurotransmitter and relative receptor do parasympathetic post-ganglionic neurones usually use
What is the exception to the usual rule of sympathetic post-ganglionic neurones being noradrenergic?
Sweat glands using ACh and muscarinic receptors
Where do sympathetic neurones synapse?
Mostly in paravertebral chain but can travel up or down chain before synapsing
How do preganglionic neurones of both sympathetic and parasympathetic divisions transmit action potentials?
Release ACh --> binds to nicotinic receptors on post-ganglionic cell --> opens ion channel --> influx of sodium --> depolarisation --> AP down neurone
How are chromaffin cells like specialised post-ganglionic symoathetic neurones?
ACh from the preganglionic neurone acts directly on the cell to release adrenaline directly into the bloodstream
What do NA and adrenaline act on?
GPCRs with no integral ion channel - adrenoreceptors
What allows for diversity and selectivity of drug action at adrenoreceptors?
Different tissues have different subtypes
How do parasympathetic postganglionic neurones transmit action potentials?
Release ACh --> binds to muscarinic receptors on effector cells (GPCRs)
What two methods of action can be used to treat asthma?
What are the sympathetic and parasympathetic effects on the pupil of the eye and their relevant receptors?
S - dilation (contract radial muscle); alpha-1
P - contraction (contracts sphincter muscle; M3
What are the sympathetic and parasympathetic effects on the airways of the lungs and their relevant receptors?
S - relax; beta-2
P - contract; M3
What are the sympathetic and parasympathetic effects on the heart and their relevant receptors?
S - increase rate and force of contraction; beta-1
P - decrease rate; M2
What are the sympathetic and parasympathetic effects on sweat glands and their relevant receptors?
S - localised secretion; alpha-1
S - generalised secretion; M3
P - no effect
Why does increased sympathetic activity to the heart not have to increase activity elsewhere?
Drive to different tissues is independent and is only coordinated when needed, e.g. fight or flight
Does the ANS initiate electrical activity in the heart?
Which preganglionic fibres transmit the parasympathetic input to the heart?
X cranial nerve - vagus nerve
Where does the vagus nerve synapse?
W/postganglionic cells on epicardial surface
W/in walls of heart at SAN and AVN
Why does parasympathetic input to the heart not really affect force of contraction?
Doesn't synapse much w/postganglionic cells in ventricles
What affect does the binding of ACh released from postganglionic cells to M2 receptors have in parasympathetic innervation of the heart?
-ve chronotropic effect
Decreased AVN conduction velocity
How does the sympathetic division innervate the heart?
Long postganglionic fibres from the sympathetic trunk innervate the SAN, AVN and myocardium --> release NA
What does binding of NA to beta-1 adrenoreceptors cause in the sympathetic input to the heart?
+ve chronotropic effect
+ve inotropic effect
What must be altered to alter pacemaker cell contraction rate?
Slow depolarising pacemaker potential
What assists the HCN channels in the action of the funny current?
T-type sodium channels
How does the sympathetic branch of the ANS act on pacemaker potentials?
Activates beta-1 receptors --> G-alpha-S activated --> stimulates adenylate cyclase --> increases cAMP --> speeds up pacemaker potential
How does the parasympathetic branch of the ANS effect the pacemaker potential?
Activates M2 receptors --> G-alpha-1 activated --> inhibits adenylate cyclase --> decreases cAMP --> increases potassium conductance --> slows down pacemaker potential
How does NA increase the force of contraction of the heart?
Beta-1 receptors activated --> increased cAMP --> PKA activated --> calcium channels activated so more calcium during action potential --> more SR calcium uptake so more CICR and increased sensitivity of contractile machinery to calcium
What is the exception to the general rule that most BV receive sympathetic innervation?
What class of receptors is present in most arteries and veins and is abundant in arterioles?
What class of receptors are found in coronary and skeletal muscle vasculature as well as alpha 1-adrenoreceptors?
How does varying the sympathetic output to vasculature alter the vasomotor tone?
Decrease = vasodilation
Normal = vasomotor tone
Increase = vasoconstriction
What is needed in vasculature in order for there to be constriction?
Basal level of contraction
What is the effect of NA and circulating adrenaline in BV w/alpha 1 and beta 2-adrenoreceptors?
NA - contraction
Adrenaline - vasodilatation
How does adrenaline cause vasodilatation at physiological concentration?
Higher affinity for beta 2-adrenoreceptors --> increases cAMP --> activates PKA --> opens potassium channels and inhibits MLCK --> relaxation of smooth muscle
How can adrenaline cause vasoconstriction at pharmacological concentrations?
Activates alpha 1-adrenoreceptors --> activates G-alpha-Q --> stimulates IP3 production --> increased calcium concentration from stores and influx --> smooth muscle contracts
What has a stronger vasodilatation effect than activation of beta 2-adrenoreceptors?
Give some examples of local metabolites.
What is more important for ensuring adequate perfusion of skeletal and coronary muscle than activating beta 2-adrenoreceptors?
What communicates changes in the state of the CVS to the brain?
What are baroreceptors?
Nerve endings in carotid sinus and aortic arch sensitive to stretch
Which two types of receptors detect low pressure and high pressure system changes in BP and alter activity of efferent nerves as a result?
High pressure side - baroreceptors
Low pressure side - atrial receptors
What is the baroreceptors reflex?
Increase mean arterial pressure detected by baroreceptors, communicated by afferent pathway to medulla --> coordinates efferent pathways in heart and vessels to cause bradycardia and vasodilatation
Which nerves do afferent fibres travel up?
What three types of drugs are used which act on the ANS?
What two types of molecule make up the sympathomimetic class of drugs?
What do sympathomimetics mimic?
Sympathetic nervous system
Name three examples of sympathomimetics.
How is adrenaline used to treat cardiac arrest and anaphylactic shock?
Cardiac arrest - vasoconstriction to maintain BP
Anaphylactic shock - stimulates alpha 1 receptors to counteract widespread vasodilatation
What method of action does Dobutamine follow?
Beta 1-agonist given in cardiogenic shock (pump failure)
How does salbutamol work?
Beta 2- agonist specific to airway of lungs to cause dilation, doesn't increase HR
Name three examples of adrenoreceptor antagonists.
How does prazonin work?
Alpha 1-antagonist --> inhibits NA action on vascular smooth muscle --> vasodilation --> antihypertensive
How does propranolol work?
Non beta1/2 selective adrenoreceptor antagonist which acts at beta 1 to slow heart rate and force of contraction and at beta 2 to cause bronchoconstriction
How does atenolol work?
Selective beta 1-antagonist given after MI to reduce cardiac workload with less risk of bronchoconstriction
Give three examples of Cholinergics.
How does pilocarpine work?
Muscarinic agonist which acts on constrictor pupillae muscle to treat glaucoma
How do atropine and Tropicamide work?
Muscarinic antagonists which increase heart rate and bronchial dilation
Can be used to dilate pupils for eye examination
How is the heart normally controlled?
Vagal control w/parasympathetic dominated control