Muscle II Cheat Sheet

typical duration of a muscle fibre action potential 2ms (same as neuronal action potentials) typical duration of the force developed by a muscle fibre after a single stimulus (aka a twitch) 20-100ms - start is delayed relative to the neuronal and muscle APs - the time it takes for the calcium concenwhy is muscle force longer than the APs? tration to rise and fall is longer than the why is it significant? events in an AP - means that muscle force can be maintained without having to continuously fire APs and expend lots of energy there may be some building in the size of the twitch because calcium concentration is increased in the cytoplasm but the twitches will be distinct the duration of an AP for contraction is much shorter than the force generated by the muscle - what will we see if we fire repeated but fairly well spaced APs? - what about if subsequent APs are arriving before the previous twitch has finished? - what about if the stimulation frequency is increased even further? summation of the twitches as the repeated stimulation is causing the calcium concentrations to reach much higher levels (the force generated by a muscle is directly proportional to the Ca2+ conc) in single twitches some of the force is absorbed by the elastic protein titin in the muscle unfused tetanus state twitches begin to merge into a smooth contraction, a state called tetanus/tetany where the muscle is at max stimulation what state do most muscles in the body operate in? tetany what is the smallest contractile unit of muscle? a motor unit (the set of muscle fibres controlled by a single motor unit) how many muscle fibres are there in a motor unit? depends on the size of the neuron 1 / 11 henneman's size principle law that states that as a muscle is stimulated to contract by a neuron in the CNS, motor units will be recruited in order of size (motor neurons that stimulate less muscle fibres will be recruited first, means that we can regulate the force of contraction and fine movements are possible) skeletal muscle types type I slow-twitch oxidative type IIa fast-twitch oxidative type IIb fast-twitch glycolytic suggest a use of type I (slow twitch) fibres posture maintenance features of slow twitch fibres - have myoglobin as oxygen store (makes them red in colour) - many mitochondria - rich supply of capillaries - very resistant to fatigue - fast myosin isoforms - capable of removing calcium from cytoplasm very quickly after contraction (high features common to both types of type II levels of SERCA pumps in their SR) (fast twitch) fibres - rapid shortening - high energy cost due to hydrolysis of ATP features of type IIa fibres (oxidative) - lots of mitochondria - pretty good blood supply - good glycogen stores - resist fatigue (higher energy cost than type I fibres) features of type IIb fibres (glycolytic) - fatigue quickly - glycolytic metabolism causes lactate accumulation and acidosis that limits contraction - don't have many mitochondria 2 / 11 - don't have a good blood supply - very high levels of glycogen true or false - individual muscles all con- false - muscles will contain a mix of diftain the same type of muscle fibre ferent fibres primarily determined by the fibre's neuronal input during development the distribution of slow/fast twitch fibres what determines the type of fibre a fibre tends to be largely genetic will become? muscle fibre differentiation is to an extent plastic and training can influence the distribution of type IIa and IIb fibres 8 the type of myosin the fibres have will how many type of myosin II can be pre- determine the myosin ATPase activity of sent in skeletal and cardiac muscle? the fibre (myosin has low ATPase activity in type I and high ATPase activity in type II) I and IIa are red (they have good blood what is the colour of each type of skeletal supply|) muscle? IIb are white what are the levels of myoglobin in each skeletal muscle type? I - very high IIa - high IIb - low relative diameters of each type of skeletal muscle fibre I - small IIa - intermediate IIb - large type IIx is referring to which of the skeletal muscle types type IIb fast glycolytic fibres what type of myosin heavy chain is expressed in type IIb muscle fibres? animals - MHC IIb humans - MCH IIx duchenne muscular dystrophy - X-linked disorder caused by a mutation in the dystrophin gene - excess calcium enters the cells and the muscle fibres die and get replaced by fat 3 / 11 or connective tissue - progressive muscle weakness prevalence of muscular dystrophy in males 1 in 3500 male births what are the treatments for DMD? no treatments what is the life expectancy of those with DMD? 25-30 what is the function of myostatin and regulate muscle growth what is the consequence of mutations to extra muscle mass and very little body fat the protein? give examples of animals that have a myostatin deficiency belgian blue cows (they have null mutations in the genes that code for myostatin) 'bully' whippets (they are homozygous for myostatin mutations) myostatin deficiency has also been found in humans - who was the most famous case of this? liam hoekstra name the contractile protein subtypes that operate within cardiac muscle what is a syncytium? a series of fused cells with their cytoplasms joined together (ie skeletal muscle) features of cardiac muscle - striations - branched syncytium - cells incompletely fused - cells joined by intercalated discs true or false - intercalated discs are structures unique to cardiac muscle true what are intercalated discs? the junctions between individual cardiac muscle cells, they contain gap junctions that electrically connect individual cardiac cells together, cells are drawn close together by desmosomes 4 / 11 - initial rising phase brought about by the opening of sodium channels (similar to neuronal APs) - broad plateau phase due to the opening of voltage-gated calcium channels which describe the action potential in cardiac inativate much slower than sodium chanmuscle nels and cause the plateau what is an excitable tissue? one that can fire action potentials (neurons, muscles) typical duration of cardiac muscle action potential 200ms relative durations of APs in neurons, skeletal muscle and cardiac muscle neurons - 2ms skeletal - slightly longer cardiac - 200ms the trigger for actin-myosin cross link formation is an increase in intracellular calcium for both muscles and 80% of the calcium comes from the SR l-type calcium channels in the muscle describe the differences in the mecha- membrane are activated unlike in skelenism of calcium release between skeletal tal, there no physical linkage between and cardiac muscle them and the ryanodine receptors in the SR cardiac muscle relies on the influx of calcium through the channel to trigger the opening of the ryanodine receptors (calcium-induced calcium release) - the contraction is myogenic (originates from within the muscle itself) skeletal muscle contraction is signalled - specialised cells in the SA node generfor by an upper motor neuron in the CNS ate a pacemaker potential, a slow depolarisation of the membrane that happens 5 / 11 on its own, when the threshold is reached initiation of APs in cardiac muscle is dif- the cells will fire and once the memferent - explain how brane potential has returned to normal the pacemaker potential begins again HCN channel (non-specific cation channel) what channel carries the pacemaker curdue to strange properties of the HCN rent? channel the pacemaker current is nicknamed the 'funny current' (If) once an action potential is initiated in the the atria are a syncytium (the cells are SA node, it spreads through the atria electrically linked) how? autonomic nervous system - sympathetic activation steepens the pacemaker potential so the threshold is reached more quickly and more APs are fired and HR is increased neuronal control over cardiac contraction - parasympathetic activation (via the vagus nerve) will have opposite effect, decrease the slope of the pacemaker potential, cell will take longer to reach threshold and heart rate will decrease which law states that the force of contraction is determined by the degree of stretch of cardiac muscle? frank-starling 1. degree of stretch - the more blood returned to the heart the more the heart stretches and this will increase the force what modulates the force of contraction of contraction (frank-starling law) in the heart? 2. autonomic nervous system - alters the cytoplasmic calcium concentration (sympathetic will increase, parasympathetic will decrease) why can the metabolism of cardiac mus- the heart must be able to beat continucle NOT be glycolytic? ously without getting cramp 6 / 11 cardiac muscle uses oxidative metabolism so what will happen if there is a short- or long- term deprivation in the blood supply (and therefore the oxygen supply)? short - angina long - heart attack smooth muscle is histologically distinct from skeletal and cardiac muscle - give examples - no striations - no t-tubules - small, spindle-shaped cells unitary - cells coupled via gap junctions difference between unitary smooth mus- and the tissue operates as a syncytium cle and multi-unit smooth muscle multi-unit - cells not coupled together and operate independently around hollow organs ie blood vessels, the gut, bladder, uterus, bronchi locations of smooth muscle and its funcfunction either to propel contents of tion those organs (gut, bladder, uterus) or regulate flow within the organ (blood vessels, bronchi) true or false - as with the other two muscle types smooth muscle contracts by the formation of actin-myosin cross bridges so the sliding filament model hold true for all three muscle types true - must remain contracted for much longer periods of time but doesn't need to operate as quickly (contracts slowly) distinct features of smooth muscle that - more energy-efficient have evolved due to the differences in - better at contracting over a wide range the requirements of smooth muscles of tensions (important for function of bladder etc) and is due to a different, less ordered arrangement of myosin and actin within the muscle - troponin is not involved - not all smooth muscle contraction is initiated by an AP differences in the role of calcium in smooth muscle contraction 7 / 11 - entry of calcium from extracellular fluid and SR is different (mechanism similar to other muscle types) - l-type calcium channels in the muscle cell membrane open in response to depolarisation and allow calcium to enter the cell - entering calcium triggers calcium-induced calcium release from the SR via ryanodine receptors (mechanism not requiring depolarisation) - activated by GPCRs in the muscle cell 3 mechanisms by which calcium enters membrane, phospholipase C cleaves the smooth muscle to trigger contraction phosphosugar head groups off membrane lipids to produce IP3 - IP3 binds to IP3 receptors (ligand-gated calcium channels) on the SR which open and allow calcium to move out the SR into the cytoplasm - when SR becomes depleted of calcium a signal is sent to channels in the muscle cell membrane called store-operated calcium channels which open to allow calcium from the extracellular fluid to move into the cytoplasm IP3 receptors inositol triphosphate is as an intracellular second messenger give examples of GPCRs in the muscle M1, M3 and M5 type muscarinic acetylcell membrane that trigger the produccholine receptors tion of IP3 role of calcium in smooth muscle the head groups of the myosin heavy chains in skeletal and cardiac muscle 8 / 11 have high intrinsic ATPase activity and regulation of muscle contraction by calci- the myosin heavy chain heads have um depends on the access of the myosin much lower ATPase activity and it is calto the actin - how is this different in cium's role to increase this activity smooth muscle? 2 heavy chains whose tails coil together myosin is a hexamer - what 6 chains is it to form an alpha helix and 4 light chains composed of? (2 regulatory and 2 essential) - calcium does not bind to troponin C and instead binds to a protein called calmodulin - calmodulin interacts with an enzyme called myosin light-chain kinase which it converts from its inactive to its active describe the regulation of contraction by form calcium in smooth muscle - myosin light-chain kinase then phosphorylates myosin's regulatory light chains which switches on the ATPase activity of the myosin heavy chain heads - leads to cross bridge formation and muscle contraction termination of the calcium signal in smooth muscle contraction - calcium removed - myosin light chain phosphatase removes the phosphate groups from the regulatory light chains true or false - some smooth muscles are myogenic true (ie gut) in some smooth muscles we can get a graded response to depolarisation (not triggered by APs) and in some, depolarisation is not even required to trigger muscle contraction - in these smooth muscles what is triggering the influx of calcium? IP3 9 / 11 - myogenic - action potentials triggered by neuronal stimulation - action potentials superimposed over mechanisms of smooth muscle excitamyogenic activity tion - can be a graded response to depolarisation (no APs) - can be modulated by neurotransmitters/hormones what regulates the cross bridges in skeletal, cardiac and smooth muscle? skeletal - troponin and tropomyosin cardiac - troponin and tropomyosin smooth - myosin light chain kinase are transverse tubules present in skeletal, cardiac or smooth muscle? skeletal - yes cardiac - sometimes smooth - no are gap junctions present in skeletal, cardiac or smooth muscle? present in cardiac and smooth true or false - the effects of nerve stimulation on skeletal muscle is always excitatory true which types of muscle can use both oxidative and glycolytic metabolism? skeletal only which types of muscle only contract in response to an action potential? skeletal and cardiac which of the types of muscle are regulat- cardiac and smooth ed by the ANS? what NS regulates the skeletal muscles regulated by the somatothers? ic NS type I/slow oxidative fibres their low rate of energy use makes them suitable for activities that require enwhich skeletal muscle fibre type has low durance or maintenance of posture myosin ATPase activity? the differences in ATPase activity are due to the myosins in different muscle fibre types containing different heavy chain isoforms 10 / 11 in a cardiac muscle action potential the initial spike involves ______ ion currents and the plateau phase is largely mediated by ______ ion channels sodium calcium which of the following is a characteristic of a fast oxidative fibre? a. high density of capillaries b. high fatiguability c. low mitochondrial density d. low myosin ATPase activity a. high density of capillaries which skeletal muscle fibre has the lowest level of myoglobin? a. fast glycolytic b. fast oxidative c. slow glycolytic d. slow oxidative a. fast glycolytic calcium-induced calcium release from the SR plays a role in excitation coupling in what types of muscle? cardiac and smooth what converts myosin light chain kinase (MLCK) from an inactive form to an active form? calcium-calmodulin 11 / 11