Autonomic Input to the Heart Flashcards
How does K+ permeability set the RMP?
- Na+/K+ ATPase (sodium pump) DOES NOT set the RMP
- The RMP is set largely due to K+ permeability of the cell membrane at rest
- Leak K+ channels are open at rest, net outflow of K+ until Ek reached.
- Only small permeability to other ions so RMP is -95mV to -85mV.
Net outflow of K+ until Ek reached.
– At Ek no net movement of potassium ions
-But RMP ≠ E as there is very small permeability to other ion species at rest. Ek = -95mV, RMP = -90mV.
How do action potentials in cardiac myocytes lead to contraction?
- Cardiac myocytes are electrically active – Fire action potentials
- Action potential triggers increase in cytosolic [Ca2+]
• A rise in calcium is required to allow actin and myosin
interaction
– Generates tension (contraction)
Describe the stages of a ventricular action potential
Describe SA Node action potentials
-Initial slope to threshold
-Activated at membrane potentials that are more
negative than -50mV
-The more negative, the more it activates HCN channels (funny current)
- Hyperpolarisation-activated, Cyclic Nucleotide-gated
channels – Allow influx of Na+ ions which depolarises the cells
How is intracellular calcium concentration of cardiac myocytes changed?
• Depolarisation opens L-type Ca2+ channels in 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
Describe the process of excitation contraction coupling in vascular smooth muscle
- Ca2+ entry leads to depolarisation
- Depolarisation opens VOCC’s. Also Noradrenaline binds to a1-receptors. (g-protein coupled) so IP3 binds to receptors on SR to release calcium too
- Cytosolic Ca2+ ions bind to calmodulin and cause a conformational change
- Calmodulin activates MLCK
- MLCK phosphorylates myosin head to allow myosin-actin interaction.
Describe ways in which contraction is regulated in vascular smooth muscle?
-Relaxation as Ca2+ levels decline (SR reuptake and exit across cell membrane-NCX AND PMCA)
– Myosin light chain phosphatase dephosphorylates the myosin light chain
Note: MLCK can itself be phosphorylated
-Phosphorylation of MLCK by PKA inhibits the action of
MLCK. Therefore inhibits phosphorylation of the myosin light chain and inhibits contraction
-MCLP dephosphorylates the myosin light chain (DAG, therefore PKC mediated)
Describe parasympathetic input to the heart
- Preganglionic fibre (10th (X) cranial nerve vagus)
- Synapse with postganglionic cells on epicardial surface, or within walls of heart at SA and AV node
- Postganglionic neurons release ACh
- Acts on M2 receptors to decrease heart rate
- Negative chronotropic effect
- Decrease AV node conduction velocity
- Motor vagus nerve (cranial nerve X, parasympathetic) innervates SA node and AV node
- Sensory vagus nerve innervates baroreceptors in arch of aorta
- Sensory glossopharyngeal (cranial nerve IX) innervates the baroreceptors in carotid sinus
Describe sympathetic input to the heart
- Postganglionic fibres from sympathetic trunk
- Innervate SA node, AV node and myocardium
- Causes release of noradrenaline
- Acts mainly on ß1 adrenoreceptors to increases heart rate
- Positive chronotropic effect
- Increases force of contraction
- Positive inotropic effect
- ß2 and ß3 receptors are also present in heart, but main effect mediated by ß1 receptors.
Describe the effect of the ANS on pacemaker potentials
- Sympathetic activity increases the slope of the pacemaker potential
- Effect mediated by ß1 receptors
- These are G-protein coupled receptors which increase cAMP production by stimulating adenyl cyclase
- As current is cyclic nucleotide dependent, so more open
- Parasympathetic activity decreases the slope. Effect mediated by M2 receptors. These are G-protein coupled receptors which increase K+ conductance and decrease cAMP by inhibiting adenyl cyclase
- K+ brings membrane potential down, further from threshold
How does noradrenaline increase force of contraction?
- Acting on ß1 receptors in myocardium, causes an increase in cAMP, which activates protein kinase A. Phosphorylation of Ca2+ channels opens them.
- Increases Ca2+ entry during the plateau of the AP
- Leads to increased uptake of Ca2+ into the sarcoplasmic reticulum
- Increase build up
- More calcium to be released
- Increase uptake reduces duration of contraction
- Necessary if need to fire heart at faster heart rate
- Leads to increased sensitivity of contractile machinery to Ca2+
- All lead to increased force of contraction
Describe the effect of the ANS on blood vessels
Most vessels receive sympathetic innervation apart from some specialised tissue such as erectile tissue.
Most arteries and veins have alpha1-adrenoreceptors (Coronary, liver and skeletal muscle vasculature also have ß2-receptors).
Circulating adrenaline has higher affinity for ß2 receptors than alpha-1 (higher noradrenaline affinity). At physiological concentration, circulating adrenaline will preferentially bind ß2 adrenoreceptors. This is vasodilatory. At higher concentrations, it will also activate alpha-1 receptors. This causes vasoconstriction (IP3 binds SR and causes increased calcium release)
Vasomotor tone allows for vasodilation to occur:
- Decreased sympathetic output leads to vasodilation
- Normal sympathetic output leads to vasomotor tone
- Increased sympathetic output leads to vasoconstriction
- Activating ß2 receptors causes vasodilation via an increase in cAMP, which activates protein kinase A. Opens potassium channels and inhibits MLCK. Leads to relaxation of smooth muscle.
Activating alpha1 adrenoreceptors causes vasoconstriction:
- Stimulates IP3 production
- Causes increase in [Ca2+]in from stores and via influx of extracellular calcium
- Causes contraction of smooth muscle
What is the role of local metabolites on vascular tissue?
Active tissue produces more metabolites:
- Adenosine
- K+
- H+
- Increase PCO2
- Local increases in metabolites have strong vasodilator effect
- More important for ensuring adequate perfusion of skeletal and coronary muscle than activation of ß2-receptors
Describe the role of baroreceptors in controlling heart rate (on low and high pressure side of CVS).
Changes in the state of the CVS are communicated to the brain via afferent nerves
- Baroreceptors on high pressure side of system
- Atrial receptors are on low pressure side of system
This alters the activity of efferent nerves
- Nerve endings in carotid sinus and aortic arch are sensitive to stretch
- Increased arterial pressure stretches these receptors
- When baroreceptors detect an increase in blood pressure, it communicates this to the medulla via the afferent pathway
- The coordinating centre of the medulla then sends efferent signals to the heart and the vessels. This causes bradycardia and vasodilation
- Counteracts the increased mean arterial pressure
What is the baroreceptor reflex?
The baroreceptor reflex maintains blood pressure over the short time by compensating for momentary changes in aBP. However it can reset to higher levels with persistently hig blood pressure.