Muscle Contraction + NMJ

motor unit

A motor neuron and all of the muscle fibers it innervates

What is the NT at NMJ? Receptor type?

Acetylcholine (ACh) Nicotinic (Cholinergic)

isometric contraction

Muscle contracts but there is no movement, muscle stays the same length tension!!

Provide examples of modulatory NTs in neuronal transmission?

NE, dopamine, adenosine

Clinical purpose of NT: prozac

SSRI (selective serotonin reuptake inhibitor) anti-depressant

why is it is advantageous for smooth muscle contraction to be slower?

maintain contraction with lower ATP cost

thick filaments contain

myosin

do all smooth muscles have action potentials?

no (e.g. vessels)

striations of muscles are ...

repeating sarcomeres

What receptors/channels are on the SR?

ryanodine receptors and release channels

Where is calcium stored in muscle?

sarcoplasmic reticulum

Curare

a drug that blocks nicotinic acetylcholine receptors, paralyzes respiratory muscles

thin filaments contain

actin, tropomyosin, troponin

What causes the falling phase of the endplate potential?

breakdown of ACh by cholinesterase, causing receptor desensitization

factors of muscle fatigue

central fatigue decreased excitability decreased Ca2+ release decreased max force decreased Ca2+ sensitivity decreased Ca2+ reuptake

Botox

cleaves SNAP/SNARE proteins (associated with synaptotagmins) which prevent neurotransmitter release --> results in temporary paralysis

what are smooth muscle contracting factors? relaxing factors?

contracting: Ca2+, rho-kinase relaxing: cAMP, CGMP

thin and thick filaments interact through what?

cross bridges (myosin head bound to actin filament)

Provide examples of inhibitory NTs in neuronal transmission?

glycine, GABA which open Cl- channels

How does sildenafil (Viagra) work?

inhibits breakdown of cGMP, which increases cGMP --> relaxation of vascular smooth muscle --> increased blood flow and erection

T tubules

invaginations of the sarcolemma that carry Ca2+ from the SR

What receptors/channels are on the T tubules?

DHP receptors and L-type Ca2+ channels

What causes delay in motor end plate response time? What increases the delay?

Delay is function of ACh release, diffusion, and activation of post-synaptic receptors. The delay is increases with distance from end plate

How is Ca2+ removed from cytoplasm after a contraction?

1. Via Na-Ca exchanger and Ca pump on plasma membrane 2. Via Ca pump on SR

How does Ca2+ enter smooth muscle cells?

1. voltage-gated Ca channels 2. store-operated Ca channels 3. IP3 receptors (GPCR) 4. ryanodine receptors

How many ACh must bind to open Na+ channels?

2 ACh bc there are two identical alpha subunits on receptor, and this is advantageous bc it makes it more difficult for spontaneous muscle activation due to random ACh binding during neuronal AP

Provide examples of excitatory NTs in neuronal transmission?

ACh, glutamate, serotonin

Why is Cl- channel activation inhibitory?

At rest, Cl- channels opening make the Vm close the E(Cl) and thus closer to threshold, which makes it more difficult to action potential to fire bc Na channels require more negative voltage to reactivate

What ion controls muscle contraciton?

Ca2+

how does Ca2+ interact with smooth muscle myofilaments?

Ca2+ binds to calmodulin, which then binds to MLCK complex resulting in a conformation change that enables ATP phosphorylation to activate myosin head for contraction! Ca2+ acts on myosin in smooth muscle not actin

how does Ca2+ interact with skeletal muscle myofilaments?

Ca2+ binds to troponin, which causes tropomyosin to move away from myosin binding site on actin once powerstroke is complete, Ca2+ releases from troponin and tropomyosin returns to original position

Clinical purpose of NT: barbituates

GABA receptor agonists anxiolytic (anti-anxiety)

Clinical purpose of NT: benzodiazapines

GABA receptor enhancer anxiolytic (anti-anxiety)

Clinical purpose of NT: strychnine

Glycine receptor antagonist performance enhancing drug

What is the quantal unit of EPPs?

MEPP

How many vesicles are in a MEPP vs. EPP?

MEPP: 1 EPP: ~200

What are MEPPs vs. EPPs?

MEPP: miniature end plate potentials in the absence of nerve AP EPP: end plate potential, which is larger and triggered by nerve AP

What advantages does a longer muscle have over a shorter muscle?

The main advantage is that a longer muscle will be able to shorten more quickly since more sarcomeres are available for shortening. Also the longer muscle can shorten in a larger extent while remaining close to the optimal length for contraction because each sarcomere will shorten less.

How does Ca2+ interact with presynaptic cell?

Upon depolarization, the presynaptic nerve opens Ca channels and Ca2+ binds to synaptotagmins and promotes fusion of vesicles and release of neurotransmitters into the cleft

do smooth muscles contain actin and myosin filaments?

YES but not sarcomeres

Clinical purpose of NT: caffeine

adenosine receptor antagonist stimulant

motor neuron pool

all the motor neurons that innervate a single muscle

long-term potentiation (LTP)

an increase in a synapse's firing potential after repeated stimulation. Believed to be a neural basis for learning and memory.

For a given rate of shortening, what factors will increase the load that can be moved?

anatomical: Increased size of the muscle (more fibers or fibrils) physiological: optimal muscle length (near resting length); increased rate of action potentials in motor nerves; increased number of motor units recruited; adequate ATP (not fatigued)

asthma + tx

asthma is caused by bronchoconstriction tx: B2 adrenergic agonists (e.g. albuterol) --> cAMP --> relax (bronchodilation)

myesthenia gravis + tx

autoantibodies attack the ACh receptors thus structural damage to NMJ tx: anti-cholinesterase (physostigmine)

Clinical purpose of NT: cocaine

blocks reuptake of dopamine, NE recreational drug

difference smooth muscle action potential vs. skeletal?

depolarization = Ca 2+ influx vs. Na+ longer duration not always controlled by APs

Clinical purpose of NT: L-DOPA

dopamine precursor pretreatment for Parkinson's Disease

fast vs. slow fibers: mitochondria

fast = few slow = many

fast vs. slow fibers: metabolism

fast = glycolytic slow = oxidative

fast vs. slow fibers: glycogen

fast = high slow = low

fast vs. slow fibers: color

fast = white slow = red (myoglobin)

maximum tensile force of muscle depends on...

muscle length 100% length (not over or under) will result in maximum tensile force and this is due to the optimal overlap positioning of myofilaments

isotonic contraction

muscle shortens and moves constant load

difference between smooth and skeletal muscle

smooth: non-striated, ANS-controlled, attached to organs skeletal: striated, voluntary control, attached to bones

strength of skeletal muscle contraction depends on...

stimulus frequency

muscle twitch

the response of a muscle to a single brief threshold stimulus (active state)

Sarcomeres consist of:

thin and thick myofilaments

Malignant hyperthermia + tx

uncontrolled release of Ca2+ from SR causing increased metabolism and heat production tx: dantrolene (Ca channel blocker)

can twitches summate?

yes

can one muscle have several fiber types? can the fiber composition change over time?

yes and yes