Striated Muscle

skeletal muscle fiber types include

slow twitch and fast twitch

which SKM muscle fiber type contracts slowly but are fatigue resistant

slow twitch

which SKM muscle fiber type contracts fast but fatigue quickly

fast twitch

which SKM muscle fiber type is good for maintaining posture

slow twitch

which SKM muscle fiber type is good for extraocular muscles to control eye movements

fast twitch

most SKMs are composed of ___

mixed fiber types

CM ___ (has or doesn’t have) slow or fast fiber types

doesn’t have

CM fiber types vary by ___

location in the heart (atria, ventricles, conduction system)

like SKM, different CM fiber types express different ___

sarcomeric protein isoforms

SKM varied fiber types adapted to ___ while CM muscle fibers vary with ___

function, location

intercalated discs are found in ___

CM (not SKM)

3 junctions of intercalated discs

desmosomes, adherens junctions, gap junctions

the ___ of intercalated discs are for strengthening connections between myocytes

desmosomes and adherens junctions

the ___ of intercalated discs are for ion transmission and electrical coupling

gap junctions

the sarcomere includes __

thin filament (actin, troponin, tropomyosin) and thick filament (myosin)

isoforms of sarcomeric proteins vary with ___ for SKM and ___ for CM

fiber type (slow vs. fast), location in heart (atrium vs. ventricle)

damaged muscle cells can release ___ into blood, which allows for measurements of these to assess muscle damage

sarcomeric proteins

__ can be used to diagnose SKM damage (rhabdomyolysis)

creatinine kinase (MM isoform)

__ are used to diagnose a myocardial infarction (ex. heart attack)

troponin isoforms

SKM is depolarized by ___, which causes ___ (ions) → ___

neural stimulation, increase in cytosolic Ca++, contraction (sliding filament mechanism)

if decrease cytosolic Ca++ → ___

relaxation

CM is depolarized by ___, which causes ___ (ions) → ___

pacemaker, increase in cytosolic Ca++, contraction (sliding filament mechanism)

SKM can be under ___ or ___ control

voluntary, reflex

release of ___ from somatic motor neuron initiates depolarization at the ___

ACh, motor end plate

SKM action potential is ___ in comparison to CM action potential

faster

CM pacemaker cell is depolarized ___

spontaneously (automaticity)

cell-to-cell action potential transmission in CM is done through ___

gap junctions

how do we couple muscle excitation to muscle contraction?

LTCCs (L-type Ca++ channel) or DHP (dihydropyridine receptor)

how does E-C coupling vary SKM between CM?

for SKM - depolarization of LTCC is sufficient for initiating E-C coupling

for CM - Ca++ influx through LTCC (or DHP receptor) is essential

how do we produce rapid E-C coupling deep in the cardiac myocyte with extracellular Ca++?

transverse T-tubules = pouches in CM sarcolemmal membrane

excitation ___ contraction

precedes (electrical events always precede mechanical events)

APD is ___ (shorter/longer) than contraction

shorter

__ is under voluntary, somatic control with depolarization beginning at the motor end plate

SKM

how do CM APs differ from SKM?

CM have longer APs

__ conduction system cells have APs that occur spontaneously

CM

CM depolarization spreads from cell to cell via __

gap junctions (found in intercalated disc)

depolarization of muscle → ___ (ions) → muscle __

increase in intracellular Ca++, contraction (E-C coupling)

T-tubules are an important site of ___, they facilitate __

E-C coupling, rapid diffusion of Ca++ into CM through activated LTCCs

T-tubule in CM is __

dyad (where T-tubule and junctional SR meet in CM)

T-tubule in SKM is __

triad (where T-tubule and 2 SR meet in SKM)

once CM depolarization causes Ca++ entry into the cell via LTCC at T-tubules, how does this lead to enough Ca++ to activate contraction of myofilaments?

by activating RyR (ryanodine receptor aka SR Ca++ release channel)

in CM: a small amount of extracellular Ca++ flows through the LTCC, triggering release of a large amount of Ca++ by activating the ___

SR Ca++ release channel (RyR, ryanodine receptor)

majority of Ca++ comes from __

SR via RyR (70-90%)

in SKM, for Ca++ to be released from SR, what is required?

LTCC and RyR physical interaction is required

STAC3 is used for ___

physical link between LTCC (or DHPR) and RyR to allow for Ca++ to be released from SR

__ mutation is linked to congenital myopathy (muscle weakness)

STAC3

STAC3 is found in ___

SKM (not CM)

CICR (Ca++ induced Ca++ release) is graded in CM, which means that a large ___ in local Ca++ is needed for ___

increase, maximum release

CICR is terminated by SR ___ acting on a ___ in the SR lumen which then ___ SR Ca++ → further __ Ca++ release from SR

Ca++, sensor, decreases, reducing

CICR is terminated by SR Ca++ acting on a sensor in the SR lumen which then decreases SR Ca++ → further reducing Ca++ release from SR

ryanodine receptors (RyR) are critical for function of ___

SKM and CM

RyR receptors is produced by varied protein isoforms: ___ in SKM and ___ in CM

RyR1 (SKM), RyR2 (CM)

RyR1 mutations can predispose to a rare disease called ___

malignant hyperthermia

Ca++ release from the SR via the Ca++ release channel (RyR) is essential for ___

contraction

in SKM, RyR is activated by ___

mechanical stimulation via the LTCC

STAC3 is the physical linker between LTCC and RyR

in CM, RyR is activated by ___

cytosolic Ca++

a small amount of trigger Ca++ enters cytosol via LTCCs → released larger amount of Ca++ from SR (CICR)

Ca++ release from SR is graded in CM, regulated by __

luminal sensor

extracellular Ca++ is ___ for initiation of E-C coupling in SKM

not required

extracellular Ca++ is ___ for initiation of E-C coupling in CM

required

excitation → ___ → ___ → ___

excitation → E-C coupling → contraction → relaxation/restitution

Now that cytosolic Ca++ has been released, how is it removed to allow muscle relaxation (ex. muscle restitution)?

SR Ca++ ATPase (SERCA) → only significant restitution mechanism in SKM (CM has others too)

why doesn’t SERCA operate continuously?

regulation/inhibition by phospholamban/sarcolipin

phospholamban (PLB) is found in ___

CM (atria and ventricles) and slow SKM

phospholamban inhibits ___ when ___

phospholamban inhibits SERCA when sarcoplasmic Ca++ is low

phospholamban releases ___ when ___

phospholamban releases SERCA when sarcoplasmic Ca++ is high → (increases Ca++ reuptake into SR)

sarcolipin is found in ___ and acts like ___

atria and in fast SKM, phospholamban

when sarcoplasmic Ca++ is low → ___

phospholamban in CM or sarcolipin in SKM inhibits SERCA

when sarcoplasmic Ca++ is high → ___

phospholamban in CM or sarcolipin in SKM released from SERCA

in CM, phosphorylation of target proteins by ___ and ___ → faster contraction (Ca++ release) and relaxation (Ca++ reuptake)

PKA, CaMK (Ca++ calmodulin dependent protein kinase)

if PKA and CAMKII phosphorylate PLB →

cause PLB release from SERCA which increases Ca++ reuptake into SR (relaxation)

if PKA and CaMKII phosphorylate LTCCs →

increase Ca++ influx

if PKA and CaMKII phosphorylate RyR, it may →

more rapid release of Ca++ from SR

what are the methods of Ca++ restitution/relaxation in CM

SERCA (SR Ca++ ATPase), trans-sarcolemmal mechanisms in CM, Ca++ retention proteins in the SR (ex. Calsequestrin and Calreticulin)

Na+-K+ ATPase is essential for ___ in CM

maintaining Na+ gradient in NCX (Na+ Ca++ exchanger)

Na+ - Ca++ exchanger (NCX) is most important trans-sarcolemmal mechanism to ___, it works by ___

reduce Ca++, exchanging 3 Na+ for 1 Ca++ (driven by electrochemical gradient for Na+ between ECF and ICF)

___ is the dominant relaxation mechanism in SKM

SERCA

___ is the dominant relaxation mechanism in CM

SERCA (75%) and NCX (24%), SL Ca++ ATPase also contributes to restitution (but not as much)

Ca++ must be ___ to allow muscle relaxation (___ in CM)

removed from cytosol, diastole

__ is essential for reuptake of Ca++ from cytosol into SR in both CM and SKM

SERCA (SR Ca++ ATPase)

SERCA has regulatory mechanisms such as ___ in CM and slow SKM, and ___ in fast SKM and possibly atria

phospholamban (PLB), sarcolipin (SLN)

__ and __ contribute to restitution

NCX, SL Ca++ ATPase (NCX is more important in CM than SKM)

phosphorylation of PLB (by PKA and CaMK) causes ___ from SERCA → ___ (ions) → ___

PLB release, increases Ca++ reuptake, relaxation

phosphorylation of LTCC (by PKA and CaMK) causes ___ (ions) → ___

increased Ca++ influx, contraction

phosphorylation of RyR (by PKA and CaMK) causes ___ (ions) → ___

more rapid Ca++ release from SR, contraction

Ca++ retention in the SR occurs via ___ in the interior of the SR

Ca++ binding proteins (ex. Calsequestrin and calreticulin)

refractory period is a period where a ___ is not possible

second AP/muscle contraction

AP is ___ than duration of contraction (muscle twitch) → therefore SKM contractions can ___

shorter, summate

increasing SKM tension in a ___ → ___ can summate

single SKM fiber, superimposed twitches

increasing SKM tension in a ___ → ___ can cause Tetanus (muscle contracts and can’t relax)

single SKM fiber, increased twitches

AP and refractory periods in CM last well into relaxation period so ___

only single twitches of CM can occur

each cardiac beat is a complete cycle of ___

contraction and relaxation (necessary to have complete cycle)

summation is ___ in CM

inappropriate (only for SKM)

how to vary contractile force of CM?

change the magnitude of Ca++ signal or Ca++ sensitivity of contractile proteins

SKM → AP and refractory period ___ than muscle twitch → contractions can ___

SKM → AP and refractory period shorter than muscle twitch → contractions can summate

CM → ___ AP and refractory period than SKM → only ___ can occur

CM → longer AP and refractory period than SKM → only single muscle twitches can occur, no summation

mechanisms for variation of tension in SKM include __

summation of twitches (can lead to tetanus) and recruiting additional motor neurons

mechanisms for variation of tension in CM include

changes in magnitude of Ca++ signal, changes in sensitivity of contractile to Ca++