CVS4 (Cellular events + ANS) Flashcards
What is responsible for setting the resting membrane potential of a cell? How is this maintained?
Cell membrane is more permeable to K+ ions (at rest), compared to other ions, due to leaky K+ channels
Na+/K+-ATPase pump
What is responsible for establishing the Na+ and K+ ion gradients between intracellular and extracellular fluid?
Na+/K+-ATPase pump
Is there a higher concentration of Na+ inside or outside a cell (at rest, in normal conditions)?
Outside cell
Is there a higher concentration of K+ inside or outside a cell (at rest, in normal conditions)?
Inside cell
Why doesn’t the resting membrane potential (of a cardiac cell) = Ek?
Because the membrane is slightly permeable to other ions, such as Na+/Ca2+/Cl-
What is the resting membrane potential of a cardiac cell (in mV)?
-90 mV
What is Ek (in mV)?
-95 mV
Which channels mediate the depolarisation of ventricular myocytes?
Voltage-gated Na+ channels
Which channels mediate the initial repolarisation of ventricular myocytes?
- Closure of voltage-gated Na+ channels
- Opening of transient outward K+ channels
Which channels mediate the ‘plateau’ type repolarisation of ventricular myocytes?
- Opening of L-type voltage-gated Ca2+ channels
- Activation of voltage-gated K+ channels
Which channels mediate the rapid repolarisation of ventricular myocytes?
- Closure of Ca2+ channels
- Activation of voltage-gated K+ channels
Which channels mediate the pacemaker potential of the SAN (Funny current)?
HCN channels (Hyperpolarisation-activated cyclic nucleotide-gated) = Na+ influx
Which channels mediate the rapid upstroke of SAN depolarisation?
Opening of voltage-gated Ca2+ channels
Which channels mediate the rapid repolarisation of the SAN?
Opening of voltage-gated K+ channels
What is the fastest pacemaker cell in the heart to depolarise?
The sinoatrial node
What are the name of the proteins in gap junctions responsible for ion movement between cardiac myocytes?
Connexins
Name the 3 ways to reduce intracellular [Ca2+] after excitation-contraction in cardiac myocytes:
1) SERCA
2) PMCA
3) Na+/Ca2+ exchanger
What must have happened to the myosin light chain to allow actin-myosin interaction?
Phosphorylation (by MLCK)
What process activates MLCK?
Ca2+ binding to Calmodulin
Name the enzyme which dephosphorylates the myosin light chain:
Myosin light chain phosphatase
Name the enzyme which phosphorylates MLCK:
Protein kinase A (PKA)
How does phosphorylation of MLCK affect its activity?
It inhibits the action of MLCK:
- Inhibits phosphorylation of the myosin light chain
- Inhibits contraction
Name the 3 tissue types which can be controlled by the ANS:
1) Smooth muscle
2) Cardiac tissue (SAN + muscle)
3) Exocrine glands
What are the 2 divisions of the ANS?
1) Parasympathetic
2) Sympathetic
From which regions of the spinal cord do the parasympathetic nerves emerge from?
- Medullary region
- Sacrum
Give the alternative name for the 10th cranial nerve:
Vagus nerve
Name the 7 regions of the body that are controlled by the vagus nerve:
1) Pharynx
2) Larynx
3) Trachea
4) Oesophagus
5) Lungs
6) Heart
7) Upper GI tract
Where does the vagus nerve originate from?
Medulla oblongata
Which branch of the ANS has short preganglionic nerves, and long postganglionic nerves?
Sympathetic NS
Which branch of the ANS has long Preganglionic nerves and short postganglionic nerves?
Parasympathetic NS
The Paravertebral chain is part of which division of the ANS?
Sympathetic NS
From which regions of the spinal cord do the sympathetic nerves emerge from?
Thoracic and Lumbar regions
Preganglionic sympathetic neurones arise from which spinal cord segments?
T1 –> L2/3
NAchR’s have an integral ion channel which is permeable to which ions?
Na+
K+
What is the endogenous agonist of a nAchR?
Acetylcholine
What neurotransmitter is produced and released from preganglionic neurones of the ANS?
Acetylcholine
What neurotransmitter is produced and released from most postganglionic sympathetic neurones?
NA
What neurotransmitter is produced and released from most postganglionic parasympathetic neurones?
Acetylcholine
What type of receptor is expressed by sweat glands?
MAchR’s (sympathetic innervation)
Why are chromaffin cells considered ‘specialised postganglionic sympathetic neurones’?
They are innervated directly by Ach released by Preganglionic sympathetic neurones, and consequently secrete Adrenaline into the circulation
What receptors are expressed by effector cells innervated by the parasympathetic system?
MAchR’s
What effect does the sympathetic system have on the pupil of the eye?
Dilation
What sympathetic receptors are expressed in the pupil of the eye?
alpha1 adrenoceptors
Which receptors are expressed in the pupil of the eye, to cause dilation?
alpha1 adrenoceptors
Which receptors in the pupil of the eye cause contraction?
M3 receptors
What effect does the sympathetic system have on the lungs?
Relaxation
What sympathetic receptors are expressed in the lungs?
beta2 adrenoceptors
Which receptors are expressed in the lungs, to cause relaxation?
beta2 adrenoceptors
Which receptors in the lungs cause bronchoconstriction when stimulated?
M3 receptors
What effect does the sympathetic system have on the heart?
Increase force of contraction (positive inotropy)
Increase heart rate (positive chronotropy)
What sympathetic receptors are expressed in the heart?
Beta1 adrenoceptors
Which parasympathetic receptors are expressed in the heart, to decrease HR?
M2 receptors
At rest, which nerve(s) innervate the heart?
Cranial nerve X (vagus nerve)
Where does the vagus nerve synapse at the heart?
SA and AV nodes (cells in epicardial surface or within walls of heart)
Which neurotransmitter does the vagus nerve release on the heart?
Acetylcholine
Where does the sympathetic nerves synapse at the heart?
SAN, AVN and myocardium
Which cranial nerve has afferent fibres from the baroreceptors in the carotid sinus?
Cranial nerve IX
Which cranial nerve has afferent fibres from the baroreceptors in the arch of the aorta?
Cranial nerve X
Which channels generate the slow depolarising pacemaker potential of the SAN?
HCN channels (hyperpolarisation-activated cyclic nuclotide-gated)
The opening of which ion channels cause the upstroke of the SAN action potential?
Fast L-type Ca2+ channels
What is the purpose of transient T-type Ca2+ channels in the SAN?
Open to push membrane potential towards threshold, to cause firing of the action potential.
The opening and closing of which ion channels causes repolariastion (and hyperpolarisation) of the SAN?
Opening of K+ channels
Closing of Ca2+ channels
How does sympathetic activity on the heart affect the funny current?
- Innervates Galpha(s) receptors
- Increases cAMP, which opens HCN channels
- Increases rate of pacemaker potential
- Shortens length of the funny current = faster depolarisation of the SAN
How does parasympathetic activity on the heart affect the funny current?
- Innervates Galpha(i) receptors
- Decreases cAMP, less HCN channels open
- Activates GIRKS = K+ efflux (slower depolarisation)
- Decreases rate of pacemaker potential
- Increases length of funny current = slower depolarisation of SAN
Why does Galpha(i) innervation cause K+ efflux?
beta and gamma subunits activate GIRKs = K+ channels = K+ efflux
How does NA increase the force of contraction of the heart?
- NA activates beta1 = Galpha(s)
- Stimulates adenylyl cyclase = more cAMP
- Activates PKA
- Opens VOCC = Ca2+ influx
- Stronger contraction possible
Which branch of the ANS innervates MOST vasculature?
Sympathetic
What type of GPCR is expressed in most vasculature?
Alpha1-adrenoceptors
Why do coronary and skeletal muscle vasculature NOT express alpha1-adrenoceptors?
Never need to constrict these vessels
Does adrenaline have a higher affinity for alpha1 or beta2 adrenoceptors?
Beta2-adrenoceptors
At physiological concentrations, which adrenoceptor expressed by vasculature will adrenaline preferentially bind to?
Beta2-adrenoceptors
How does beta2-adrenoceptor activation cause vasodilation?
Galpha(s) activation =
- increased cAMP
- PKA activation
- opening of GIRK channels = K+ efflux
How does alpha1-adrenoceptor activation cause vasoconstriction?
Galpha(q) activation =
- IP3 production
- Ca2+ release from SR and Ca2+ influx from outside cell
= increased intracellular [Ca2+] = contraction of smooth muscle
How do active tissues ensure they have adequate blood perfusion?
- Produce more metabolites (H+/CO2/K+/adenosine)
- Have strong vasodilator effect
Name 4 metabolites produced by active tissues, which have a vasodilator effect on the surrounding vasculature:
1) H+
2) K+
3) Adenosine
4) Increased pCO2
Where are the 2 important locations of arterial baroreceptors in the CVS?
1) Carotid sinus
2) Aortic arch
Where is the carotid sinus?
At the bifurcation point of the common carotid arteries (into the internal and external carotid arteries)
Baroreceptors in the carotid sinus relay information to the medulla via which cranial nerve?
Cranial nerve IX (Glossopharyngeal nerve)
Baroreceptors in the aortic arch relay information to the medulla via which cranial nerve?
Cranial nerve X (Vagus nerve)
What do arterial baroreceptors detect?
Changes in mean arterial pressure
If arterial baroreceptors detect a rise in mean arterial pressure, what does the medulla do in response?
1) Reduce heart rate
2) Reduce vasoconstriction (vasodilate)
What is meant by ‘sympathomimetics’?
Drugs producing the same physiological effects as the sympathetic nervous system, by promoting the stimulation of sympathetic nerves.
Which sympathomimetic drug is commonly used to treat asthma?
Salbutamol
Which adrenoceptors does Salbutamol bind to, and is it an agonist or antagonist?
Beta-2 agonist
Describe the action of propranolol:
Beta antagonist
- Decreases sympathetic activity on heart
= Reduces HR + contractility
You want to try to reduce a patients hypertension, but they also suffer from asthma. Do you prescribe propranolol or atenolol, and why?
Atenolol
- It is a cardio-selective beta-1 antagonist
- Propanolol is a non-selective beta-1 antagonist, so may worsen asthma (may cause bronchoconstriction)
Which suffix is usually given to beta antagonist drugs?
- olol
ie: Propanolol, Atenolol, Metoprolol etc.
Name a parasympathomimetic used in Glaucoma treatment:
Pilocarpine
How does Pilocarpine reduce the effects of Glaucoma?
Parasympathomimetic:
- Activates constrictor papillae muscle
= Increases outflow of aqueous humour from the eye, reducing intraocular pressure
What is Tropicamide used for?
To dilate the pupil of the eye for examination/surgery
Name a muscarinic antagonist, used to dilate the pupil of the eye for examination:
Tropicamide
Name the 5 uses of Atropine:
1) Treat bradycardia
2) Treat organophosphate insecticide or nerve gas poisonings
3) Treat some kids of heart block
4) Reduce saliva production during surgery
5) Treat some gastrointestinal disorders (smooth muscle relaxant)
Is Atropine a short- or long-acting muscarinic antagonist?
Long-acting antagonist
Atropine and Tropicamide block what kind of receptor?
Musarinic GPCR’s
