Mam Phys Exam 1

Gs cAMP Pathway

• activated alpha subunit —> adenylyl cyclase → converts ATP to cAMP

• increases intracellular cAMP levels

• cAMP acts as second messenger

• cAMP activates cAMP dependent protein kinsases (protein kinase A)

• protein kinases —> phosphorylate another protein —> causes cellular response —> magnifies cascade

Gt pathway

• phosphodiesterase (activated bt Gt)

• converts cAMP —> AMP (non-signaling molecule)

• decreases intracellular cAMP, thus reduced amount of second messenger

• inhibits cell activity

Gq pathway

• alpha-q portion binds to membrane bound Phospholipase C

• splits a membrane phospholipid PIP —> IP3 and DAG

  • DAG: directly activates protein kinase C

  • IP3: causes release of calcium from ER

    • Ca2+ acts are third messenger and directly binds to calmodulin to activate protien kinases to increase that cell’s activity

Arachidonic acid pathway

• precursor - in membrane bilayer G protein g mechanism

• Phopholipase A2 converts to Arachidonic acid

• enzymes (COX=cyclooxygenases) act to produce prostoglandins (inflammation, uterine contractions, etc.)

• thromboxans also produced

  • lipooxygenases (convert arachindonic acid to leukotrienes)

ICF

• low Na

• high K

• low Cl

• low Ca

• hi Pr

Cl wants to follow concentration gradient but is repelled by

Pr

K leaks out but held by

negative charge

Na wants to follow concentration gradient but repelled by

K

hyperkalemia

• lots of K in ECF

• less K leaving the cell

• more positive charge within the cell

• more depolarized

• can reach threshold better

hypokalemia

• less K in ECF; more in ICF

• leaks out to ECF more than usual

• makes cell more negatively charged

• hyperpolarized

sequence

1) wave of depolarization

2) VR calcium channels open, Ca enters, synaptic vesicles exocytose NT into synaptic cleft —> diffuse across

3) NT bind to receptor of CR channel

4) if CR channel —> Na enters, following conc. grad.

5) diffuse across the cell body; start depolarizing; if only some NT, and only some channels, Na/K pump can restore RP

6) if all the way across axonal hillock w/ enough Na to reach threshold, VR Na+ channels open —> AP

graded potentials

• CR

• dendrites, cell body

• depolarizing or hyperpolarizing

• depends on strength/frequency

• degrades

• local current (diffusion)

action potential

• VR

• axonal hillock, axon

• depolarizing in effect

• all or nothing

• doesn’t degrade

• continuous conduction or saltatory

hypernatremia

• excess Na+ in ECF; usually dehydration; cell shrinks

hyponatermia

• lower than usualy Na+ in ECF —> too hydrated —> resting potential hardly changes

hypercalcemia

• excess Ca2+ in ECF —> decrease excitability of membrane —> doesn’t alter RP or threshold

• mechanically blocks pores —> when extracellular Ca2+ is incresased —> keeps Na+ from entering and thus hinders reaching threshold to generate an AP

hypocalcemia

• lower Ca2+ in ECF —> increases excitability of membrane

tetrodotoxin

• antagonist

• binds to VR Na+ channels

• cant depolarize —> no AP

saxitoxin

• antagonist

• binds to and blocks VR Na+ channels

• can’t depolarize —> no AP

dendrotoxin

• antagonist (goes against what should happen)

• blocks VR K+ channels

• prolongs AP duration

• makes it harder to repolarize

Lidocaine

• antagonist

• blocks VR Na+ channels and inhibits conduction of AP

Anatoxin-A

• agonist

• binds to CR Na+ channels in cell body/dendrites

• enhances/mimics response

• no mechanism to end it

• channels stay open and Na+ floods in continuously

• can’t repolarize

• contraction without relaxation

T-tubules run parallel between two bags of terminal cisternae

triad

A band during contraction

wont change length

I band during contraction

only thin; depends on contraction; could be wider or narrower —> greater contraction = more narrow

H zone during contraction

only thick; depends on contraction; wider/narrower —> greater contraction = more narrow

titin

spring that anchors myosin to Z lines and provides elasticity

nebulin

spans length of thin filament; supports and measures

dystrophin

anchors sarcomeres to sarcolemma

muscle contraction

1) wave of depolarization

2) VR Ca2+ channels open, Ca2+ enters

3) synaptic vesicles exocytose ACH

4) ACH goes across neuromuscular junction binds to CR Na+ channels in the motor endplate of the sarcolemma

5) CR Na+ channels open, Na+ enters, depolarizing sarcolemma

6) wave of depolarization, causes VR Na/K channels in sarcolemma to generate an AP

synaptotagmin

vesicle membrane; Ca2+ sensor

synaptobrevin

vesicle membrane

SNAP 25

terminal membrane

Syntaxin

terminal membrane

Neuromusclar still

1) AP down T-tubules

2) DHP receptors cause configuration change

3) uncorks Rynodine receptors (which are Ca2+ channels)

4) dumping Ca2+ on underlying sarcomeres

5) 80% of Ca2+ from terminal cisternae stores

myosin binding stuff

1) low energy configuration - has ATP bond to it

2) when myosin binding site revealed - myosin head attracted to it

3) myosin binds actin —> acts as ATPase —> splits off P — releases energy

4) myosin head does a power stroke, moving actin

5) myosin head binds new ATP, detaches, back to #1, will bind again, if tropomyosin out of the way

how to stop muscle contraction

• stop the stimulus

• Neuronal VR Ca2+ channels close; Ca2+ pumps at synaptic terminal pump out Ca2+ —> synaptic vesicles

• Acetylcholinesterase in neuromuscular junction

• breaks down ACH and more free ACH broken down = more comes off receptors to be broken down

• CR Na+ channels close —> Na/K pumps re-establish RP

• VR channels close Na, K, Ca

• Calcium umps in terminal cisternae and sarcolemma, resequester Ca

• decrease levels of ICF calcium

• troponin not binding to Ca2+, reverts to OG configuration; tropomyosin covers myosin binding sits on the actin

type 1

• many blood capillaries and mitochondria

• aerobic metabolism

• red in color because of Ig concentrations

• resistant to fatigue

• slow to contract

• slow to relax

• doesnt generate as much force

• first recruited

type 2a

• some mitochondria

• less extensive capillaries

• still reddish

• most aerobic

• high level of glycogen and glycolytic enzymes

• intermediate contraction time and tension generated

• second recruited

type 2b

• white in color, generally

• very few mitochondria

• very little myoglobin

• MANY MANY glycolytic enzymes

• anaerobic

• not resistant to fatigue

• strongest contraction force

• fastest contraction

  • third recruited

temporal/wave summation

• incomplete tetanus

• increase rate of stimulation until relaxation phase completely lost

• tetanus = smooth top = peak temporal summation

• peak tension a muscle can generate occurs when all motor units are contracting in complete tetany

treppe

• shouldn’t happen, but does

• allow relax before next stimulation but get a higher tension generated

• muscle not warmed up —> Ca2+ pumps not efficient at re-sequestering Ca2+

• gradual accumulation of Ca2+ = more and more myosin heads able to bind

black widow spider venom

• level 1

• presynaptic

• massive release of ACH

• agonist

• severe cramps and spasms

physostigmine

• level 2

• synaptic cleft

• ACHase inhibitor

• agonist

neostigmine

• level 2

• agonist

• synaptic cleft

• ACHase inhibitor

• reduced active ACH receptors cause progressive muscle weakness and problems with breathing

nerve gas/sarin

• level 2

• synpatic cleft

• agonist

• ACHase inhibitor

• prevents breakdown

insecticides

• level 2

• synaptic cleft

• agonist

• organophosphates

anatoxin a

• level 3

• post synaptic

• agonist

nicotine

• level 3

• post synaptic

• low doses

• agonist

botulin

• antagonist

• level 1

• pre-synaptic

• blocks release of ACH = damages release mech (SNARE)

curare

• level 3

• post synaptic

• antagonist

• blocks ACH receptors

• doesnt cause AP

• non-depolarizing blocker

succynylcholine (SUX)

• antagonist

• level 3

• post synaptic

• binds receptors but allows one AP and then blocks it

• depolarizing blocker

TETANUS IS CNS

• toxin enters CNS

• inhibitory neuron that produces GABA

• damages SNARE

• synaptic vesicles cant release GABA

• no relaxation of antagonistic muscles

• isometric contraction

• no movmeent/action

muscle relaxants works centreally too

• flexeril

• skelaxin (metaxalone)

• SOMA

DMD

• can’t make function dystrophin

  • dystrphin anchors myofibrils to sarcolemma

maliganant hyperthermia

• SR RYR receptors (ca2+ channels) are locked open and Ca2+ uncontrollably released

• treatment = dantrolene that blocks RYR receptors = inhibits release of Ca2+ from SR

smooth muscle cells do not have

troponin; t-tubules’ SR not well developed

phasic contraction of smooth muscle

usually relaxed and then contraction

tonic contraction of smooth muscles

usually contracted; sphincter; allows things to pass contraction varies as needed

contraction of smooth muscle

1) since no t-tubules, spread of Ca2+ is slower and Ca2+ binds with calmodium

2) Ca2+ calmodium complex activates Myosin light chain kinase phosphorylates myosin light chain

3) increases ATPase activity

4) crossbirdge formation/contraction

relaxation of smooth muscle

1) calcium pumped out to ECF or SR

2) Ca detaches from calmodium

3) less Ca calmodium complexes = less actvation of MLCK, less myosin ATPase activity, more MLC phosphotase activity

4) dephosphorylation of myosin light chain

5) muscle relaxes

smooth muscles maintain contraction

without fatiguing

Gprotein activates phospholipase C to split

PIPs to IP3 and DAG

IP3 opens

SR and relases Ca

VR ca channels

ligand gated channel; allow enough Ca in to spark Ca release from SR