Essay On Autonomic Regulation Of The Heart Notes

Autonomic regulation of the heart

mechanisms of contraction

-cardiac muscle is an electrical synctium- intercalated discs- Gap junctions and desmosomes, action potentials propagate through these gap junctions

-action potentials travel down the T tubules which have travel radially, but unlike skeletal muscle travel axially aswell

-During the plateau phase of action potential in ventricles, calcium influx through L type voltage gated calcium channels which is important for excitation-contraction coupling.

-Excitation-contraction coupling- requires Ca influx through L type Ca channels unlike skeletal muscle where there is mechanical coupling- calcium induced calcium release when calcium binds to Ryanodine receptors

-the calcium binds to cardiac isoform of troponin C – TNNC1. The Ca-TNNC1 releases the inhibition of the cardiac isoform of troponin I on actin. The tropomyosin filaments bound to cardiac troponin T to shift away. This allows myosin to interact with the active sites on the Actin

ATP fuels cross bridge cycling and thick filaments slide past the thin filaments and generates tension.

Relaxtion of the cardiac muscle

1. extrusion of calcium into the extracellular fluid

-when the membrane potential returns to more negative values, and the calcium concentration falls

-Na/Ca exchanger which pumps 3 sodium in and one calcium out

-Sarcolemmal calcium pump

2. reuptake of calcium from the cytosol by SR

-calcium pump in the sarcoplasmic reticulum.

-unlike skeletal muscle the SR calcium pump is inhibited by phospholamban. When phosphorylated by cyclic dependent protein its ability to inhibit SR calcium pump is lost

3. dissociation of calcium from Troponin C

-as calcium concentrations fall, calcium dissociates from troponin C and blocks the actin myosin interactions and causes relaxation. Adrenergic agonists increase the rate of relaxation by promoting phoshphorylation of troponin I which enhance the dissociation of calcium from troponin C.

-increase in calcium increase the strength of contraction

Sympathetic input to the heart

-post ganglionic fibres of the cardiac nerves release noradrenaline- innervates the SA node, Atria, Ventricles

-right cardiac nerve-more effect on heart rate , left cardiac nerve-more effect on contractility

-at rest the firing rate is less than vagus nerve

-effect: increase Heart rate and contractility

-noradrenaline binds to B1-adrenergic receptors- trimeric G protein dissociates into As and By subunits. The As subunit activates a membrane bound adenylate cyclase and catalyses the conversion of numerous ATP into cAMP- amplification along pathway means the activation of a single adrenoceptor generates a large number of intracellular messenger molecules

- activated Camp-protein kinase A-phosphorylates various proteins

Chronotropic effects

-pacemaker cells: cAMP-positive allosteric effect on HCN4 and increases the open-state probability-greater funny current- greater pacemaker current means the threshold is reached quicker-faster rate of contraction-positive chronotropy

-SA node myocytes the increase in Ca current accelerates the SAN reaching threshold generating action potential

-increase in AV node conduction velocity-dromotropic effect – reduces the time lag between SA node and ventricular contraction and in an ECG shortens the PR interval.

-the protein kinase A also phosphorylates delayed rectifier K channels- increases the probability they are open- resulting increase in repolarising outward current leads to the shortening of ventricular action potentials- reduction in action potential duration means more excitations fit into each minute shortens the QT interval- increase chronotropy

Ionotropic effects

-Camp-activates the intracellular enzyme protein kinase A- protein kinase A catalyses the phosphorylation of the α1 subunits of L-type calcium channels which increases the open state probability and duration

-In atrial and ventricular myocytes there is an increase in plateau calcium current- greater influx of calcium means there is more cross bridge cycling - greater intracellular calcium ion concentration, more trigger calcium-more calcium induce calcium release from SR-increase contractility positive ionotropic effect- there is also direct binding of As subunit

-there is also an increase in Ca²⁺ sensitivity through the phosphorylation of troponin C

-protein kinase A phosphorylates phospholamban and reduces the inhibitory effect on Ca2+-ATPase of the sarcoplasmic reticulum. The disinhibition increases the Ca affinity of the pump and boosts calcium transfer from sarcoplasm into sarcoplasmic reticulum-increase Calcium uptake-increase Ca stores-enlarged calcium store-means more calcium can be released on activation- -phosphorylation of ryanodine receptor- increases their open probability-increase calcium release from SR-increase contractility

-increase in calcium current through T type and L type voltage gated calcium channels-decrease in threshold for action potential?-pacemaker depolarises it quicker- faster rate of contraction-increase in chronotropy

Lusitropic effect –myocardial relaxation

-faster Ca reuptake by the sarcoplasmic reticulum-duration of the contraction falls and relaxation rate increases. This shortens the ejection and isovolumetric relaxation phases of the cardiac cycle-minimises the reduction in diastolic interval (makes the diastolic interval as long as possible)- this is important as the heart needs sufficient time to refill- this is done through...

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