CVS4 (Cellular events + ANS) Flashcards by Megan Scotcher

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

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What is responsible for establishing the Na+ and K+ ion gradients between intracellular and extracellular fluid?

Na+/K+-ATPase pump

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Is there a higher concentration of Na+ inside or outside a cell (at rest, in normal conditions)?

Outside cell

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Is there a higher concentration of K+ inside or outside a cell (at rest, in normal conditions)?

Inside cell

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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-

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What is the resting membrane potential of a cardiac cell (in mV)?

-90 mV

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What is Ek (in mV)?

-95 mV

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Which channels mediate the depolarisation of ventricular myocytes?

Voltage-gated Na+ channels

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Which channels mediate the initial repolarisation of ventricular myocytes?

Closure of voltage-gated Na+ channels

- Opening of transient outward K+ channels

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Which channels mediate the ‘plateau’ type repolarisation of ventricular myocytes?

Opening of L-type voltage-gated Ca2+ channels

- Activation of voltage-gated K+ channels

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Which channels mediate the rapid repolarisation of ventricular myocytes?

Closure of Ca2+ channels

- Activation of voltage-gated K+ channels

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Which channels mediate the pacemaker potential of the SAN (Funny current)?

HCN channels (Hyperpolarisation-activated cyclic nucleotide-gated) = Na+ influx

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Which channels mediate the rapid upstroke of SAN depolarisation?

Opening of voltage-gated Ca2+ channels

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Which channels mediate the rapid repolarisation of the SAN?

Opening of voltage-gated K+ channels

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What is the fastest pacemaker cell in the heart to depolarise?

The sinoatrial node

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What are the name of the proteins in gap junctions responsible for ion movement between cardiac myocytes?

Connexins

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Name the 3 ways to reduce intracellular [Ca2+] after excitation-contraction in cardiac myocytes:

1) SERCA
2) PMCA
3) Na+/Ca2+ exchanger

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What must have happened to the myosin light chain to allow actin-myosin interaction?

Phosphorylation (by MLCK)

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What process activates MLCK?

Ca2+ binding to Calmodulin

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Name the enzyme which dephosphorylates the myosin light chain:

Myosin light chain phosphatase

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Name the enzyme which phosphorylates MLCK:

Protein kinase A (PKA)

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How does phosphorylation of MLCK affect its activity?

It inhibits the action of MLCK:

Inhibits phosphorylation of the myosin light chain
Inhibits contraction

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Name the 3 tissue types which can be controlled by the ANS:

1) Smooth muscle
2) Cardiac tissue (SAN + muscle)
3) Exocrine glands

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What are the 2 divisions of the ANS?

1) Parasympathetic

2) Sympathetic

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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?

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