Flashcards in Cardiophysiology Deck (32):
Describe the function of skeletal, cardiac and smooth muscles along with the calcium they rely on and their ATP source.
Skeletal - ambulation, posture, displacing load, glucoregulation
Calcium source: intracellular
ATP: is stored as glycogen, sarcoplasmic stores, phosphocreatine, glycolysis, oxidative phosphorylation, fatty acids
Cardiac: moving blood
Calcium source: extra and intracellular
ATP source: oxidative phosphorylation and fatty acids
Smooth: change lumen diameter, digestion and controlling blood pressure
Calcium source: extra and intracellular
ATP source: oxidative phosphorylation.
Describe the tropomyosin, three troponin complex.
Troponin I: anchors to actin
Troponin C: binds to calcium
Troponin T: anchors to tropomyosin
Tropomyosin binds to myosin heavy chains.
Describe the start of a voluntary motor function until the point of neuromuscular junction.
The signal starts in the motor cortex of the cerebral cortex. Then the signal travels down the spinal cord through the rubrospinal, reticulospinal tracts, into the ventral root, where it travels via alpha, gamma motor neurons and contacts skeletal muscle at the neuromuscular junction.
What happens at the neuromuscular junction?
What happens at the cleft?
The action potential travels down the axon and at the nerve terminal, it opens voltage dependent calcium channels.
Calcium activates vesicular fusion and exocytosis of acetylcholine.
Acetylcholine will bind to cholinergic, nicotinic receptors which itself is a ligand gated sodium channel. This will produced a highly localized action potential known as the end plate potential that travels distally and activates a voltage gated sodium channel on the sarcolemma to produce a action potential.
Acetylcholine is broken up by cholinesterase.
The action potential is trasmitted to the skeletal muscle cell, now how does muscle contract?
The positive current travels down the T-tubule and this will activate DHPR coupled with RyR (receptors of the sarcoplasmic reticulum) serves as a functional calcium channel. This releases the intracellular calcium stores.
From there the calcium travels to the myofilaments and it will bind to troponin C. Tropomyosin blocks binding sites on ATP that myosin can bind to. When troponins unbinds tropomyosin, the conformation changes and reveals binding sites. This allows myosin bound to ATP to bind to actin. Immediately the ATP is hydrolyzed by ATPase in the light chain and the powerstroke occurs. Then it releases ADP and instantly rebinds ATP.
Describe the process of muscle relaxation.
Minor: NCX (sodium calcium exchanger) on the sarcolemma efflux of calcium and influx of sodium)
Primarily: SERCA - sarco/endoplasmic reticulum Ca2+ ATPase. SERCA is always retuning calcium to the SR. It's just that when DHPR and RyR stop, SERCA wins out.
What is the inotropic state?
IT refers to how cardiac muscle can have different gradations of contraction that is directly proportional to calcium levels.
How is cardiomyocyte contractility controlled ionically?
Type L Calcium channel: allows for calcium influx. (extracellular calcium)
NCX: brings sodium in and calcium out
Na+/K= ATPase will bring sodium out of the cell and potassium in as to allow the NCX to function.
How is calcium concentration in plasma controlled
Its controlled by the parathyroid glands which sense blood calcium levels. They secrete a hormone, PTH. PTH causes calcium release from bones and calcium is absorbed by the kidneys and released. Plasma calcium will regulate cardiac muscle excitability.
What is hypocalcemia? '
What is hypercalcemia?
It is caused by low calcium levels. Hypoparathyroidism, kidney failure and vitamin D deficiency.
Counterintuitive: there is hyperexcitability of neurons with a low calcium levels.
This is because voltage gated sodium channels which increases sodium current.
Hypercalcemia is caused by hyperparathyroidism.
It causes neuronal hypoexcitability. This is because it raises the threshold for voltage gated sodium channels.
What is afterload, preload, isometric, and isotonic.
Afterload is the weight that muscle is going against.
preload is the potential force generated by the muscles.
When afterload = preload, this is isometric, there is no displacement of load and no work is done.
When the contractile force overcomes load, there is work being done and work generates power.
Isotonic is when the load is displaced and work is displacing the load.
How is muscle tension generated?
It done through twitches. Which summate in with increases in frequency until to become a fused tetanus which is sustained fusion of muscle twitches that allow whole muscle to contract.
What is passive tension, what is active tension?
Passive tension is the tension generated from stretching muscle from resting length.
Active tension is when muscles contract. Tension is highest initially at the start of contraction but decreases with shortening of muscle because there is less actin to grab onto.
What is type 1 muscle fiber?
What is type 2 muscle fiber
what happens during muscle contraction?
Type 1 is for endurance, it is oxidative and well vascularized, slow twitch, small diameter
Type 2 is for powerful movements, its anaerobic, less vascularized, large diameter and fast twitch.
Type 1 is the first to respond for the initial contraction (slow twitch+isometric) then it recruits the Type 2 which are needed for too heavy load and the powerful contraction, over time (reaches isotonic), 50 msec the type 2 taper off and type 1 is largely recruited and takes over.
What is negative repetition?
Negative repetition are reps of eccentric contractions. It is a lengthening contraction, in the quadriceps.
It is basically a controlled lengthening because the load is higher than the muscle force.
How do we monitor contraction in our brain?
The golgi tendon organs (GTO) are stress sensors in the tendon.
Motor neurons innervate the muscle but Type Ib afferents bring information from the GTO to tell the brain if the stretch or contraction tension is okay.
What happens when GTO senses a damaging tension?
Two things happen.
It will lead to the activation of inhibitory interneurons which will shut down the alpha motor neurons to stop contraction of the ipsilateral agonist muscles.
it will lead to stimulation of stimulatory interneurons to activate alpha motor neurons that stimulate ipsilateral antagonist muscles that oppose contraction.
How do muscle spindles monitor change in length and rate of change in length?
When muscle stretches or contracts, intrafusal fiber (bag fibers) will sense the change and the rate of the change which leads to increased firing up the Ia afferent to the brain. Type II afferents are firing when muscle length is resting. The gamma motor neurons that synapse on chain fibers will stretch or contract the intrafusal fiber to maintain the critical tension so that it can still be able to sense change.
When it reaches its tension limit, contraction stops.
What is hypertrophy?
What is hyperplasia?
What changes occur in response to muscle work?
Hypertrophy: increase in muscle fiber diameter
(sufficient protein within 2-3 h post workout)
(if muscle protein synthesis is greater than muscle protein breakdown, then hypertrophy will occur).
Hyperplasia: increase in number of muscle fibers
More myofibrils, vasculature, mitochondrial enzyme content, glycogen stores, secretion of myokines.
What do satellite cells do?
Satellite cells are usually not activated but they will be activated in response to injury. Satellite cells will form myoblasts.
The myoblasts will fuse to form a multinucleated myotube which will fuse with myofibers.
THis is the main source of muscle growth and regeneration.
What are the benefits of exercise? (increased myokines)
improved insulin sensitivity (improved glycemic control)
Lipid metabolism (obesity)
-lipolysis in adipose tissue,
-glucoregulatory peptides (small intestines)
-better revascularization of regions (blood pressure)
What are anabolic factors that aid in muscle growth and repair?
Anabolic adrogenic steroids are testosterone and dihydrotestosterone - (which activate Andorgen receptors leading to anabolic and anticatabolic (inhibition of glucocorticoid receptor) effects
Stimulate satellite cell proliferation
Stimulate growth hormone secretion (proteogenesis and stimulates IGF-1 production)
Stimulate insulin-like growth factor-1 (IGF-1) expression.
(synergizes with GH, proteogenesis, and regeneration/satellite cell mitosis)
Calcium signaling (ca2+/CaM phosphatase, CaMKI,) mediate hypertrophic growth.
Describe the GH + IGF-1 pathway in regards to glucose and fatty acid levels.
GH+IGF-1 would cause lipolysis of fat as fuel for skeletal muscle.
It would also cause amino acid reuptake by the skeletal muscle and protein synthesis.
Prevent: the break down of glycogen, protein breakdown and glucose uptake from glycogen stores.
Describe muscle catabolism
Too much calcium, too much cortisol leads to muscle wasting.
Calcium influx into skeletal muscle will activate calcium dependent proteases (calpains)
Glucocorticoids (released by immune/antiinflammatory responses and stress) will have proteolytic effects to maintain blood glucose levels via the GR.
Cortisol will inhibit IGF1 so it can't have muscle protein synthesis, cortisol will increase proteolytic factors, muscle type II fibers will atrophy, promote myostatin/GDF-8 (expressed in satellite cells and impedes muscle growth)
Myostatin - will block proliferation of satellite cells.
Describe the process of muscle fatigue.
The brain sense muscle fatigue. It sends signals down chemo and nociceptors to secrete neurotransmitters and lower the ability of motor neurons.
Muscle work produces protons (lactic acid) which will lower the ability of muscle to cross bridge cycle and lower levels of calcium in the sarcoplasm.
Free radicals, peroxide, and ROS will impede cross bridge cycling.
ATP from glycogen stores will decrease these stores and potassium efflux from tubules will prevent action potentials and disrupt the gradient.
Describe anaerobic metabolism.
Glycogen is broken down into lactate and protons.
Lactate and protons do not have significant effects on fatigability with protons have a more modest reduction on tetanic force. But no effect on fatigability.
Increased proton concentration affects calcium levels.
The muscle fiber most likely to be affected is the type II fibers that are anaerobic.
What is sarcopenia?
it is loss of muscle mass due to age. This will specifically only affect your type II fibers.
Alot of factors can cause this:
GH/IGF-1, loss of satellite cells, loss of anabolic androgens, inactivity, not enough protein in diet, loss of motor innervations
Overtime testosterone will decline by 1% every year after 30
and GH will decline 14% every decade after age 20.
Describe smooth muscle and its contraction.
It is controlled by autonomic neurons, muscle beds contract as multiunit- one synaptic output but muscle fibers act independently for finer control.
Muscle undergoes slow wave potentials and spike potentials, voltage gated calcium channels open, goes above threshold, calcium influx, potassium channels open and voltage gated calcium channels close (hyperpolarization)
Visceral smooth muscle undergoes plateau potentials.
Smooth muscle has multidimensional shortening while skeletal is just two dimensional. (multiunit)
Smooth muscle is widely dependent on extracellular calcium and so influx will be mediated by Type-L calcium channels and voltage independent calcium channels.
Relaxation occurs the same way with pumping of calcium out and storing a little.
So to promote constriction, inhibit SERCA.
Describe pacemaker (SA node) and plateau potentials (myocardium, smooth muscle of GI, uterine)
Pacemaker you have three currents. A funny Na+ current, a T-type calcium channel current, a potassium leak. Slowly you depolarize...
Then BAM calcium takes over! This causes sharp depolarization. At around 0 the funny current closes, then type T closes.
VOLTAGE gated potassium channels opens and repolarization occurs.
Plateau involves many kinds of isoforms. Sodium channel opens first. Rapid depolarization. Then a potassium channel opens and you start repolarizing but then..
Calcium channel opens along with sodium influx and You stall. Then an isoform of potassium voltage gated channel opens and you finish repolarization.
How does lidocaine work?
It blocks voltage gated channels of the nociceptors. If they can't have action potentials, you can't get action potentials of PAIN to the dorsal root and to the brain.
What are inotropic and metabotropic transmission.
Metabotropic at SA node example
Metabotropic is slower because it is G-coupled.
Ionotropic is just ligand activates the ion channel and you get depolarization or hyperpolarization.
Metabotropic. - ligand binds, then activates a signal cascade with the G protein activating the ion channel to induce something.
Acetylcholine activates a G protein which activates a potassium outward rectifying channel. So you are decreasing firing making it harder to reach threshold and so sinus rhythm is stretched and times between beats is slowed.