Lecture 5.1 - The Autonomic Nervous System PDF

Location - General: ◦Sympathetic: ‣ Thoracolumbar outflow ‣ T1-L2 ◦Parasympathetic: ‣ Craniosacral outflow ‣ CN III, VII, IX, X, S2-S4 ◦Both sympathetic and parasympathetic NS contain afferent and efferent nerve fibers, which consist of pre-ga...

Location - General: ◦Sympathetic: ‣ Thoracolumbar outflow ‣ T1-L2 ◦Parasympathetic: ‣ Craniosacral outflow ‣ CN III, VII, IX, X, S2-S4 ◦Both sympathetic and parasympathetic NS contain afferent and efferent nerve fibers, which consist of pre-ganglionic and post-ganglionic neurones ANS and CVS: ◦The ANS controls: ‣ Heart rate ‣ Force of contraction of the heart ‣ Peripheral resistance ◦The ANS does not: ‣ Initiate electrical activity in the heart Parasympathetic innervation of the heart: ◦Fibres of PNS originate in the vagal motor nuclei ◦Travel to the thoracic cavity in right and left vagal nerves ◦Synapse in with postganglionic parasympathetic neurones within myocardium ◦Innervates: ‣ SA node ‣ AV node ‣ Little/none to ventricles Sympathetic innervation of the heart: ◦Fibres from SNS innervate the whole heart ◦Originate in T1-T5 ◦Synapse at paravertebral sympathetic ganglia ◦Post-ganglionic fibres run with great vessels to reach heart ◦Innervates: ‣ Ventricles ‣ Atria ‣ SA and AV node Chronotropic effects: ◦SNS - positive chronotropic: ‣ Faster and shorter SA node phase 4 (increase slope) ‣ Norepinephrine stimulate β1 adrenergic receptors ‣ Activates funny Na+ channels - increasing rate of SA node ‣ Therefore increases the frequency of heart rate ◦PNS - Negative chronotropic:  ‣ Slower SA node phase 4 (decrease slope) - action potential is slower ‣ Acetylcholine stimulate muscarinic (M2) receptors ‣ Inactivate funny Na+ channels and activates outward flow of K+ currents (hyperpolarises cells) ‣ Therefore decreases the frequency of heart rate Dromotropic effects: ◦SNS - positive dromotropic: ‣ Increase in conduction velocity via AV node ‣ Activate L-type Ca++ channels - calcium uptake increases Protein Kinase A phosphpyrylates L-type Ca2+ channels - responsible for phase 0 ‣ Shortens effective refractory period - as Na+ channels are already activated by the SNS ‣ AV nodal cells recover earlier from inactivation ◦PNS - Negative dromotropic: ‣ Decrease in conduction velocity via AV node ‣ Inactivate L-type Ca++ channels ‣ Prolongs effective refractory period ‣ If severe, can lead to heart block - as action potential ij.int cannot move from SA to AV AMP pka AP node and down to ventricles Noradrenalin Adenyloghase Noddendylase Acetylcholine Inotropic effects - affects on contractile cells: ◦SNS - positive inotropic: ‣ Norepinephrine stimulate β1 adrenergic receptors ‣ Activate L-type Ca++ channels ◦PNS - Negative inotropic: ‣ Effects on atria - as action potential goes to SA node ‣ Acetylcholine stimulate muscarinic (M2) receptors ‣ Inactivate L-type Ca++ channels e PKA  Autonomic effects on vasculature: ◦Most blood vessels receive sympathetic innervation ‣ Exceptions: e.g. erectile tissue have parasympathetic innervation ◦Most arteries and veins have alpha-1- adrenoreceptors ◦Binding of norepinephrine to alpha-1: SMC contraction and vasoconstriction ‣ Gαq subunit activation→ IP3→ mobilises Ca++ from sarcoplasmic reticulum Vasomotor tone of blood vessels: ◦Key role in maintaining total peripheral resistance ◦There is always a base level of sympathetic activity in all blood vessels and not parasympathetic Some blood vessels have beta-2 receptors: ◦Coronary, skeletal muscles, liver also have β2 receptors, in addition. ◦Activating β2 causes vasodilation in contrast to alpha 1 (Chronic stress can lead to vasoconstriction) ◦Circulating epinephrine has higher affinity to β2 but at higher concentrations it will activate alpha-1 adrenoreceptors. ◦Mechanism of epinephrine- β2 mediated vasodilation: ‣ Gs→ CAMP→ PKA→ inhibits MLCK→ vasodilation ‣ MLCP inhibits contraction, so activates relaxation