CVS S4 - The autonomic nervous system and the CVS Flashcards
How is the resting membrane potential generated in cardiac cells?
- At resting potential, K+ channels are open meaning the membrane is permeable to K+ ions
- Movement of K+ ions out of the cell, down their concentration gradient established by the Na+-K+-ATPas and towards Ek creates a more negative voltage inside the cells
- Resting potential = -90mV
Describe the phases of ventricular action potentials
- Depolarisation occurs as Na+ channels open
- Membrane potential increases to +20mV
- Transient repolarisation occurs as voltage gated K+ channels open
- Plateau phase as L-type Ca2+ channels open calcium influx equals potassium efflux
- Repolarisation occurs as there is large K+ efflux and calcium channels become inactivated
Why does the cardiac muscle action potential peak at +20mV and not reach ENa?
Depolarisation stimulates the inactivation of voltage-gated sodium channels
What is the starting membrane potential in a pacemaker cell action potential?
-60mV
What are the ion channels responsible for the upstroke and downstroke of the pacemaker cells action potential?
Upstroke - Voltage gated calcium channels open
Downstroke - Voltage gated potassium channels open
What channel is responsible for the gradual depolarisation to threshold of the pacemaker potential and which ions flow through this channel?
- HCN (hyperpolarisation- activated cyclic nucleotide gated channel)
- Enables influx of sodium ions into the cell
Name the current created by the HCN channel and what does it do (depolarise?repolarise?etc)
If - Funny current
Gradual depolarisation of pacemaker cell to threshold -40mV
Outline the process of excitation-contraction coupling that occurs in the ventricular myocardium
- Increase in intracellular calcium as depolarisation opens L-type calcium channels
- This in turn stimulates calcium-induced-calcium-release (CICR)
- Calcium bind to ryanodine receptors on the sarcoplasmic receptors releasing Ca2+ form SR stores
- Calcium ions then bind to TnC (troponin) subunit on tropomyosin
- Stimulates conformational change exposing myosin binding site on actin molecule
- Sliding filament mechanism
Name an inhibitor of MLCK (smooth muscle excitation contraction coupling)
Protein kinase A (PKA)
Which enzyme opposes the action of MLCK? (smooth muscle excitation contraction coupling)
MLCP - Myosin light chain phosphorylase dephosphorylates the myosin head light chain
How are intracellular calcium levels returned to normal in cardiac myocytes?
- Pumped back into the SR via SERCA
- Some exits the cell across the sarcolemma via PMCA or NCX
Where is the control centre for total peripheral resistance situated?
Vasomotor centres in the medulla oblongata in the brainstem
What two components make up control of total peripheral resistance?
Sympathetic nervous system and local metabolites
List some organs with high vasomotor tone
Skin, skeletal muscle, gut
What causes a decrease in vasomotor tone in skeletal muscle during exercise?
- Mainly due to local release of vasodilator metabolites
- Partly due to specialised vasodilator response to circulating levels of adrenaline mediated through beta-2-adrenoceptors
Outline concentration coupling in vascular smooth muscle
- Initiated by depolarisation (opening voltage gated calcium channels) or activation by alpha 1 adrenoceptors (G alpha q subunit)
- G alpha q activated phospholipase C
- Cleaves PIP2 to forms IP3 and DAG
- IP3 bind to receptors on sarcoplasmic receptors releasing calcium
- Calcium binds with calmodulin which together as a complex activates myosin light chain kinase (MLCK)
- MLCK phosphorylated the myosin light chain allowing myosin cross bridge to bind actin filament and allow contraction to occur
- DAG activate protein kinase C which inhibits the effects of myosin light chain phosphatase (MLCP) which normally breaks the myosin cross bridge
Describe the differences between where neurones of the parasympathetic and sympathetic divisions synapse
Sympathetic- with post-ganglionic neurones in the paravertebral chain
Parasympathetic- with neurone in ganglia close to the target tissue
How do nicotinic receptors on post-ganglionic neurones differ from muscarinic and adrenoreceptors
Nicotinic receptors have an integral ion channel
Adrenoreceptors and muscarinic receptors are G-protein coupled so have no integral ion channel
What neurotransmitter molecule binds to muscarinic receptors?
Acetylcholine
What is the parasympathetic input to the heart?
Pre-ganglionic fibres- 10th Cranial nerve (Vagus nerve)
What receptors does the parasympathetic input act on and what are its general effects?
- M2
- Decreases heart rate (negative chronotrophic effect)
- Decreases AV node conduction velocity
What is the sympathetic input to the heart?
Post-ganglionic fibres from the sympathetic trunk
What receptors do sympathetic input in the heart act on and what are its general effects?
- Acts on beta-1-adrenoreceptors
- Increases heart rate (positive chronotrophic effect)
- Increases force of contraction (positive inotrophic effect)
How does the sympathetic nervous system increase the speed of pacemaker potentials?
- Mediated by beta-1-adrenoreceptors
- Increases levels of cAMP
- Causes more HCN channels to open
- Increases the speed of depolarization
How does the parasympathetic nervous system decrease the speed of pacemaker potentials?
- Mediated by M2 receptors
- Increases K+ conductance and decreases cAMP
How does the sympathetic nervous system increase the force of contraction in heart muscle?
- Noradrenaline acts on beta-1-adrenoreceptors in myocardium (G alpha s)
- Increases cAMP
- In turn activates PKA
- Causes phosphorylation of Ca2+ channels meaning they remain open for longer and so more calcium ions enter the cell during the action potential
- Increases the force of contraction
Which type of adrenoreceptor would be found in the majority of arteries and veins?
Alpha-1
What effects does alpha-1 receptors in the vasculature mediate?
- At pharmacological levels of adrenaline IP3 production is stimulated which increases calcium release from stores and causes increase efflux into the cell
- Stimulates vasoconstriction
What type of adrenoreceptor would be found in coronary and skeletal muscle blood vessels?
Beta-2-adrenoreceptors
What effect do beta-2 adrenergic receptors found in skeletal and coronary blood vessels mediate?
- Respond to circulating levels of adrenaline
- Increases cAMP
- Activates PKA
- Opens K+ channels and inhibits MLCK
- Causing vasodilation
Describe the location and function of baroreceptors
- High pressure side of system in carotid and aortic sinus
- Excitation occurs by stretching under high pressure which is transmitted to the medulla oblongata via afferent nerve fibres
Describe the function of the atrial volume receptors
- Low pressure baroreceptors
- Increase in volume is transmitted to the hypothalamus
- Decreases production of ADH (vasopressin)
- Leads to loss of water via urine, decreasing circulatory volume
List three classes of drugs with important functions in the CVS
- Sympathiomimetics
- Adrenoreceptor antagonist
- Cholinergics
What is the function of dobutamine and what receptors would the drug act on?
Beta-1 agonist
Given in cardiogenic shock
Give an example of a sympathiomimetic drug used outside the CVS and outline its function
Salbutamol
Acts on beta-2-adrenoreceptors in treatment of asthma
Which drug would be given in the treatment of glaucoma and which class does this belong to?
Pilocarpine
Muscarinic agonist
What is the function of prazosin?
Inhibits noradrenaline action on alpha-1 adrenoceptors causing vasodilation
What are the functions of muscarinic antagonists?
Increase heart rate, bronchial dilation and dilate pupils for examination
List two beta-adrenoreceptor antagonists and explain how they differ
Propanolol- non-sensitive so acts on both beta 1 and 2 receptors
Atenolol- specific to beta 1 receptors, reduces risk of bronchioconstriction
How does the parasympathetic nervous system cause constriction of airways of the lung and what counteracts this effect?
- Acetylcholine binds to M3 receptors causing constriction
- Circulating adrenaline causes dilation by binding to beta-2 adrenoreceptors
List the effects of the sympathetic nervous system on the liver and how these effects are mediated
Noradrenaline stimulates glycogenolysis and gluconeogenesis by binding to alpha and beta-2 adrenoreceptors
How does the action of the sympathetic nervous system differ between sweat glands on the palms of the hands from the rest of the body?
- Sweat glands in the hand are stimulated by circulating adrenaline binding to alpha adrenoreceptors
- Sweat glands located around the rest of the body are stimulated by acetylcholine binding to cholinergic muscarinic receptors
