Session 4 Flashcards
Describe the membrane permeability changes and ionic currents underlying the ventricular and pacemaker cell action potential
Ventricular cells - upstroke due to v-gated Na+ channels opening (influx of Na+), initial repolarisation due to transient outward K+, plateau due to L-type Ca2+ channels opening (influx of Ca2+), repolarisation due to K+ channels opening (efflux of K+)
Pacemaker cells - initial slope due to funny current, HCN channels open (influx of Na+), upstroke due to opening of voltage gated Ca2+ channels opening (Ca2+ influx), downstroke due to opening of v-gated K+ channels (efflux of K+)
Describe the processes which generate the resting membrane potential of cardiac cells
RMP set by K+ permeability. K+ ions move out of the cell down their concentration gradient making the inside more -ve relative to the outside. As charge builds up an electrical gradient is established.
Describe, in general terms, the processes of excitation-contraction coupling in ventricular myocardial cells
Influx of Ca2+, calcium induced calcium release from Ryanodine (SR). Ca2+ binds to troponin C, conformational change in tropomyosin to expose myosin binding sites on actin filaments (sliding filament mechanism)
Describe the factors influencing the changes in intracellular free calcium concentration of ventricular cells during the action potential
Depolarisation opens L-type Ca2+ channels in T tubule systems, CICR
Relaxation - Ca2+ pumped into SR (SERCA), PMCA, NCX
Describe the membrane potential changes in pacemaker cells associated with increases and decreases in heart rate
Increased heart rate - sympathetic nervous system acts on SAN, noradrenaline (acting on B1 receptors) speeds up the heart rate by making the pacemaker potential steeper
Decreased heart rate - parasympathetic nervous system acts on SAN, acetylcholine (acting on M2 receptors) slows the heart rate by making the pacemaker potential shallower
Describe the mechanisms which control contraction of vascular smooth muscle cells
Ca2+ binds to calmodulin (4Ca2+ binds to 1 calmodulin) which activates MLCK (myosin light chain kinase). This phosphorylates the light chain on myosin heads to permit action with actin, leading to contraction.
As Ca2+ levels decline, relaxation occurs.
Phosphorylation by PKA inhibits MLCK.
Describe the cellular mechanisms controlling heart rate in the normal heart
Sympathetic increases heart rate by increasing gradient of the pacemaker potential slope. GPCR (Gs) increases cAMP which causes protein kinase A to phosphorylate Ca2+ channels.
Parasympathetic decreases heart rate by decreasing gradient of the pacemaker potential slope. GPCR (Gi) decreases cAMP and increases K+ conductance.
Baroreceptors in the carotid sinus and aorta are sensitive to stretch (high pressure) and atrial receptors are sensitive to low pressure.
Describe the critical anatomical features of the autonomic nervous system, such as the existence of ganglia, and divisions into pre- and post-ganglionic neurones
ANS divides into sympathetic and parasympathetic nervous system.
The ganglion is a collection of cell bodies.
There are two neurones arranged in series (pre- and post-ganglionic). The cell body of the pre-ganglionic neurone is in the CNS.
Describe the key anatomical features of the sympathetic and parasympathetic branches of the ANS, including where pre- and post-ganglionic fibres leave the CNS, the location of ganglia and the relative lengths of pre- and post-ganglionic fibres
Sympathetic - thoracolumbar origin, pre-ganglionic neurones arise from T1-L3, pre-ganglion short, post-ganglionic long, pre- releases ACh, post releases NA.
Parasympathetic - craniosacral origin, pre-ganglionic fibres travel in cranial nerves or sacral outflow from S2-S4, pre-ganglion long, post-ganglion short/within target tissue, pre and post both release ACh
List the structures innervated by each of the sympathetic and parasympathetic systems, and in broad terms, describe the effect of the sympathetic or parasympathetic activity upon these structures
Structure/sympathetic/parasympathetic:
Pupil/dilate/constrict
Airways of lung/dilate/constrict
Heart/increase rate and force/decrease rate and force
Sweat glands/localised secretion/no effect
Blood vessels in skeletal muscle/dilate/constrict
Name the usual chemical transmitters at the synapses between pre- and post-ganglionic neurones in each of the sympathetic and parasympathetic branches, and the type of receptors upon the post-ganglionic cell body
Sympathetic:
Pre - ACh, post - NA, adrenoceptor
Parasympathetic:
Pre - ACh, post - ACh, muscarinic receptor
State in broad terms the distribution of different types of adrenoceptors around the body
a-receptors are found on vascular smooth muscle
B-receptors are found in the heart, smooth muscle of the airways of the lung, adipose tissue, blood vessels in skeletal muscle
State the action of the sympathetic nervous system on blood vessels in different organs
Increased blood flow to skeletal muscle, heart, brain
Decreased blood flow to gut, skin
Explain the action of the sympathetic and parasympathetic system upon heart rate and force of ventricular contraction
Sympathetic:
Noradrenaline –> B1 receptors –> increase in cAMP –> protein kinase A phosphorylates Ca2+ channels –> increased Ca2+ entry –> increased rate and force of contraction
Parasympathetic:
Acetylcholine –> M2 receptors –> decrease AVN conduction velocity –> decreased rate
