CVS Session 4 - Cellular and Molecular Events in the CVS and Control by the ANS Flashcards Preview

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Flashcards in CVS Session 4 - Cellular and Molecular Events in the CVS and Control by the ANS Deck (26):

Describe how the resting membrane potential of cardiac cells is generated.

- K+ permeability sets the RMP 
I. Cardiac myocytes are permeable to K+ ions at rest
II. K+ ions move out of the cell – down their concentration gradient.
III. Small movement of ions makes the inside negative with respect to the  outside.
IV. As charge builds up an electrical gradient is established

- RMP does not exactly = Ek
I. Net outflow of K+ until EK reached
II. At EK no net movement
IV. EK = -95mV, RMP = -90 to -85 mV
V. Very small permeability to other ion species at rest


NB. Cardiac myocytes have lots of different types of K+ channels. Each behaves in a different way and contributes differently to the electrical properties of the cells.


State the RMP for the axon, skeletal muscle, SAN and cardiac ventricle.

- Axon: -70 mV

- Skeletal muscle: -90 mV

- SAN: -60 mV

- Cardiac ventricle: -90 mV


Outline the ventricular action potential.

- Depolarisation – Na+ influx

- Initial repolarisation – K+ efflux

- Plateau – Ca2+ influx

- Proper repolarisation – K+ efflux)


Outline the SAN action potential 

- Initial slope to threshold – If (funny current)

- Activated at membrane potentials that are more negative than - 50mV

- The more negative, the more it activates

- HCN channels

I. Hyperpolarisation-activated, Cyclic Nucleotide-gated channels

II. Allow influx of Na+ ions which depolarises the cells


- Upstroke – opening of voltage-gated Ca2+ channels

- Down stroke (repolarisation|) – opening of voltage-gated K+ channels


Briefly describe the action potentials throughout the heart, with reference to speed. 

- SA node is fastest to depolarise, it is the pacemaker and sets rhythm

- Other parts of the conducting system also have automaticity (slower)


Briefly describe some action potential diagrams in different parts of the heart. 

- SA node 

- Purkinje fibres 

- Atrial muscle 

- Ventricular muscle 

- AV node 


Explain the problems that could occur during the process of excitation leading to contraction. 

- The triggering of a single action potential which spreads throughout the heart is responsible for contraction

- If action potentials fire too slowly → bradycardia

- If action potentials fail → asystole

- If action potentials fire too quickly → tachycardia

- If electrical activity becomes random → fibrillation


Describe the factors influencing the changes in intracellular free calcium concentration of ventricular cells during the action potential.

- Each action potential initiated at the SA node produces a single heartbeat. The action potential spreads through the conduction system and between cardiac myocytes via gap junctions.

- Intracellular Ca2+concentration rises during the plateau phase, in small part because of Ca2+ crossing into the cell via Ca2+ channels, and in large part because of release of Ca2+from intracellular stores.

- As Ca2+ concentration rises this triggers various mechanisms tending to remove Ca2+ from the cytoplasm.

- These include re-uptake into intracellular stores and the expulsion of Ca2+ from the cell in exchange for inward movement of Na+ - 'sodium calcium exchange'.


Outline the contraction of blood vessels. 

- Arteries and veins have smooth muscle cells within the tunica media of the vessel walls.

-Contraction of these vascular smooth muscle cells leads to an increased tone of the vessel, narrowing the lumen.

- Contraction is initiated by phosphorylation of myosin light chains by myosin-light chain kinase.

- An increase in intracellular Ca2+ causes formation of a Ca2+- calmodulin complex which activates myosin –light chain kinase (MLCK).


Provide a brief overview of hyperkalaemia and hypokalaemia. 

- Plasma [K+] must be controlled within a tight range – 3.5 – 5.5 mmol L-1

- If [K+] is too high or low it can cause problems, particularly for the heart

- Hyperkalaemia – Plasma K+ concentration is too high > 5.5 mmol L-1

- Hypokalaemia – Plasma K+ concentration is too low < 3.5 mmol.L-1

- K+ permeability dominates the resting membrane potential


Outline the effect of hyperkalaemia, the risks associated with it, the severity of these risks and the treatment for it. 

- Effect:

I. EK becomes more positive (smaller concentration gradient), so membrane potential becomes less negative and depolarises

II. Depolarisation of the membrane causes Na channels to open then inactivate, which means less are available for upstroke (less steep uptake slope)

III. HCN channels are activated by hyperpolarisation. So if potassium is high, the cell is relatively polarised and therefore these channels will remain inactive. Depolarisation is slow and over a long duration.


- Risks:

I. Pacemaker potential decreases, heart rate decreases or stops (asystole)

II. May initially get an increase in excitability but then conductance may cease


- Severity: depends on extent and how quickly it develops

I. Mild 5.5 – 5.9 mmol/L

II. Moderate 6.0 – 6.4 mmol/L

III. Severe > 6.5 mmol/L


- Treatment

I. Calcium gluconate

II. Insulin + glucose

These won’t work if the heart already stopped


Outline the effect of hypokalaemia, the risks associated with it, the severity of these risks and the treatment for it. 

- Action potential is prolonged (graph is wider with slower repolarisation)

- Delays depolarisation and can lead to early after depolarisations (EADs) 

- The plateau phase is prolonged so calcium channels remain open for longer. Thus, there is more opportunity to stimulate more action potentials and cause more contractions

- This can lead to oscillations in membrane potential which can result in ventricular fibrillation. 


Outline excitation-contraction coupling. 

- Depolarisation opens L-type Ca2+ channels in the T-tubule system 

- Localised Ca2+ entry opens Calcium-Induced Calcium Release (CICR) channels in the SR 

- Close link between L-type channels and Ca2+ release channels 

- 25% enters across sarcolemma, 75% released from SR 


Outline the regulation of cardiac myocyte contraction. 

- As with skeletal muscle 

- Ca2+ binds to troponin C

- Conformational change shifts tropomyosin to reveal myosin binding site on actin filament 

(Refer to sliding filament mechanism)


Explain the relaxation of cardiac myocytes.

- Must return [Ca2+]i to resting levels

- Most is pumped back into SR (SERCA) – Raised Ca2+ stimulates the pumps

- Some exits across cell membrane

I. Sarcolemma Ca2+ATPase (PMCA)

II. Na+ /Ca2+ exchanger (NCX)


Outline the Autonomic Nervous System in terms of its functions, its ability to regulate physiological functions and what it exerts control over. 

- Functions

I. Regulates physiological functions e.g. BP

II. Where parasympathetic and sympathetic divisions both innervate a tissue they often have opposite effects.

III. Sympathetic activity is increased under stress

IV. Parasympathetic system is more dominant under basal conditions


- Important for regulating many physiological functions

I. Heart rate, BP, body temperature… etc (homeostasis)

II. Co-ordinating the body’s response to exercise and stress

III. Largely outside voluntary control


- Exerts control over

I. Smooth muscle

II. Exocrine secretion

III. Rate and force of contraction in the heart


Detail the neurotransmitters and receptors involved in the autonomic nervous system.

- The action of the parasympathetic system on heart rate is mediated via acetylcholine acting on M2 muscarinic receptors.

- The action of the sympathetic system on heart rate and contractility is mediated via noradrenaline acting on β1adrenoreceptors. Adrenaline from the adrenal medulla also acts on the heart.

- Sympathetic drive to different tissues is independently regulated.


Outline the ANS control of the cardiovascular system. 

- The ANS controls:

I.Heart rate

II.Force of contraction of heart

III.Peripheral resistance of blood vessels

IV. Amount of venoconstriction


- The ANS does not initiate electrical activity in the heart

I. Denervated heart still beats, but at faster rate

II. At rest the heart is normally under vagal influence


Outline the parasympathetic input to the heart.

- Preganglionic fibres - 10th (X) cranial nerve VAGUS

- Synapse with postganglionic cells on epicardial surface or within walls of heart at SA and AV node

- Postganglionic cells release ACh

- Acts on M2 -receptors

I. Decrease heart rate (negative chronotropic effect)

II. Decrease AV node conduction velocity


Outline the sympathetic input to the heart.

- Postganglionic fibres from the sympathetic trunk

- Innervate SA node, AV node and myocardium – Release noradrenaline

- Acts mainly on β1 adrenoreceptors

I. increases heart rate (positive chrontropic effect)

II. increases force of contraction (positive inotropic effect)

NB: β2 and β3 adrenoreceptors are also present in the heart, but the main effect is mediated by β1 receptors.


Outline action potentials in the pacemaker cells. 

-Cells in the SA node steadily depolarise toward threshold

I. Slow depolarising pacemaker potential

II. Turning on of slow Na+ conductance (If – funny current)

III. Opening of Ca2+ channels


- AP firing in the SA node sets the rhythm of the heart


Outline the effect of the ANS on pacemaker potentials. 

- Sympathetic activity increases the slope. 

I. Sympathetic effect is mediated by β1 receptors.

II. GPCRS increase cAMP which speeds up the pacemaker potential. 


- Parasympathetic activity decreases the slope. 

I. Parasympathetic effect is mediated by M2 receptors. 

II. GPCRS increase K+ conductance and decrease cAMP. 


Explain how noradrenaline increases the force of contraction. 

- NA acting on β1 receptors in myocardium causes an increase in cAMP ® activates PKA

I. Phosphorylation of Ca2+ channels increases Ca2+ entry during the plateau of the AP.

II. Increased uptake of Ca2+ in sarcoplasmic reticulum.

III. Increased sensitivity of contractile machinery to Ca2+


- All lead to increased force of contraction


Outline some clinical applications by referring to drugs acting on the ANS. 

- Sympathomimetics

I. α-adrenoceptor agonists

II. β-adrenoceptor agonists


- Adrenoceptor antagonists

I. α-adrenoceptor antagonists

II. β-adrenoceptor antagonists


- Cholinergics

I. Muscarinic agonists

II. Muscarinic antagonists


Describe the mechanisms which control the contraction of vascular smooth muscle cells. 

- Sympathetic activity causes constriction of arterioles –vasoconstriction (mediated via α1adrenoreceptors).

- There is constant activity in the sympathetic nervous system (sympathetic vasomotor tone) tending to make arteriolar smooth muscle contract. The tone varies from organ to organ.


Explain the role of the autonomic nervous system in controlling peripheral resistance.

- Vascular tone in skin and skeletal muscle is also a mechanism for controlling total peripheral resistance. Sympathetic outflow to blood vessels is controlled from the brainstem - via the 'vasomotor' centres in the medulla oblongata.


- The parasympathetic branch of the ANS can act on specialised blood vessels such as in erectile tissue to cause vasodilation. However, it indirectly causes vasodilation in organs such as the gut by its stimulating activity of the organ which in turn causes the release of local vasodilator mediators.