SM01 Mini4 Flashcards Preview

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Flashcards in SM01 Mini4 Deck (117):
1

synapse

structure in which a chemical or electrical signal is passed between neurons or from neuron to a muscle fiber

2

synaptic transmission

process by which neurotransmitters are released by a neuron into a synapse, binds & activates receptors on another neuron or a muscle fiber

3

neuromuscular junction

junction of axon terminal w/a motor end plate on a muscle fiber 

4

motor endplate

region of muscle fiber plasma membrane that lies directly under axon terminal

5

endplate potential

depolarizations of skeletal muscle fibers caused by binding of neurotransmitters

6

list correct temporal sequence of events in chemical neurotransmission

  • action potential starts at axon hillock & travels w/saltatory propagation down axon 
  1. AP depolarizes axon terminal
  2. depolarization of axon terminal opens voltage-gated Ca2+ channels & Ca2+ enters terminal
  3. Ca2+ causes vesicular membrane fusion ACh release
  4. ACh binds receptors on motor endplate 2:1 & opends cation ion channel
  5. Namoves in at a faster rate than K+ moves out & causes depolarization

7

describe recycling of presynaptic vesicle

clathrin-mediated endocytosis

dynamin GTPase separates vesicle from plasma membrane

vesicle fuses w/other unfilled vesicles in axon terminal

8

describe recycling & formation of ACh

remaining ACh in synaptic cleft degraded by ACh esterase→ removed acetyl group

choline reuptake by axon terminal

cholinacetyltransferase forms ACh from recycled Ch

9

what is the difference between an endplate potential & an action potential in skeletal muscle?

an action potential depolarizes causes muscle contraction

endplate potential is a depolarization specifically at the endplate, graded potential that may or may not be above threshold to cause an action potential

10

what are the possible sites for blocking neuromuscular transmission? list an example of each.

  1. neuronal Na+ channel
    • tetrodotoxin & saxitoxin
  2. Ca2+ channel
    • omega-conotoxin
  3. K+ channel
    • dendrotoxin
  4. ACh release
    • tetanus toxin & botulinum toxin
  5. AChR cation channel
    • d-tubocurarine & alpha-bungarotoxin
  6. Muscular Nachannel
    • tetrodotoxin, saxitoxin, & mu-conotoxin
  7. AhCesterase
    • physostigmine & DFP (difluorophosphate)

11

what specific action does Ca2+ perform when it enters the axon terminal?

binds & transforms synaptotagmin so that vesicular membranes can fuse w/plasma membrane for ACh release

12

what protein(s) are responsible for holding vesicles to the plasma membrane?

synaptobrevin in vesicle membrane

syntaxin & SNAP-25 in plasma membrane of axon terminal (axolemma)

13

what is a quantum & what is its effect at the motor endplate?

quatum is the contents of a single vesicle= 10,000 ACh molecules

endplate potential of 1mV

14

where are neuromuscular junctions located?

near center fo muscle fiber & action potential will spread in both directions

15

16

most commonly used drugs for muscle relaxation during sx

ACh antagonist (d-tubocurarine) & agonist (succinylcholine)

17

steps of excitation-contraction coupling

  1. action potential transmitted from synaptic terminal to sarcolemma @ NMJ to transverse tubule
  2. T-tubule action potential→ produces mechanical connection between DHP receptors (on tubule membrane) & Ryanodine receptor (on sarcoplasmic reticulum membrane)→ opening of Ryanodine receptor→ release of Ca2+​ to cytosol
  3. Ca2+ release initiates mechanical contraction

18

role of sarcolemma

invaginations create transverse tubules

19

role of transverse tubule

bring sarcolemma in close contact w/SR membrane

houses DHP receptors

20

role of sarcoplasmic reticulum

sequestering Ca2+ at concentration 2x of extracellular & 10,000x cytosolic

21

isometric contraction

constant length contraction

NO shortening, but increase in tension

velocity=0; external work=0

22

isotonic contraction

constant tension contraction

shortening of muscle fibers, but NO change in tension

velocity>0; external work>0

muscle develops force= to load being lifted

23

dihydropyridine receptors

aka DHP receptor

voltage-gated Ca2+ channel

action potential→ depolarization of sarcolemma of T tubule→ DHP opens & Ca2+ enters cell→ conformational change induces conformational change & opening of Ryanodine receptor

24

Ryanodine receptor

in membrane of sarcoplasmic reticulum

mechanically activated Ca2+ channel protein

activated by conformational change in DHP-R of T-tubule membrane

25

where is Ryanodine ligand activated instead of mechanically activated?

cardiac muscle

DHP present in cardiac muscle fibers but not coupled to Ryanodine to induce conformational change

26

structure of troponin

  • troponin T binds single moleculeof tropomysin
  • troponin C binds Ca2+: 2 pairs of sites
    • higher affinity pair is always has bound Ca2+
    • lower affinity pair binding results in movement of troponin complex
  • troponin I binds actin & inhibits contraction

27

structure of myosin II

hexamer of 2 heavy chains, 2 alkali chains, & 2 regulatory chains

heavy chain regions: rod, hinge, & HEAD x2

28

what is the function of the 2 heads of myosin?

each has a binding site for actin & another site for hydrolyzing ATP

heads alternate actin binding to walk along actin filament

29

what is the function of alkali light chain of myosin?

to stabilize the head region of the heavy chain

30

what is the function o fthe regulatory light chain of myosin?

regulates ATPase activity of head region

also site of troponin regulation via phosphorylation by either Ca2+-dependent or independent kinases

31

What happens when Ca2+ binds the pair of low affinity binding sites?

Ca2+ from sarcoplasmic reticulum

  1. TnI detaches from F-actin binding site→ permits tropomyosin movement
  2. TnT pushed away from myosin binding site on actin→ induces cross-brdige cycling

32

What else can be found bound in the high affinity Ca2+ binding sites of troponin?

Mg2+

33

Steps of cross-bridge cycling

  1. resting state: myosin regulatory light chain is phosphorylated & head region of heavy chain is boudn to ADP
  2. head region binds actin→ conformational change
  3. phosphate release→ POWER STROKE (filaments slide past each other)
  4. ADP is release
  5. ATP binds head region→ dissociation from actin
  6. hydrolysis of ATP→ myosin returns to rest state
    • released phosphate binds TnI

34

factors effecting cross-bridge cycling

  • availability or concentration of Ca2+
  • availability or concentratin of ATP
  • rate of ATPase determines speed of cycling

35

in skeletal muscle, how does relaxation occur?

reuptake of Ca2+ into sarcoplasmic reticulum via Ca2+-ATPase pump

36

calsequestrin

calcium binding protein found in sarcoplasmic reticulum

increases amount of calcium sequestered in sarcoplasmic reticulum

37

purposes of ATP in muscle contraction

  1. myosin power stroke
  2. dissociation of myosin from actin
  3. power Ca-ATPase pump

first two are same molecule of ATP

38

sources of cellular ATP

  1. free ATP in cytoplasm: small, only enough for a few contractions
  2. transfer of phosphate from creatine phosphate (PCr) to ADP: supplied 4 ATP/min
    • limite supply of PCr
    • recycling of creatine requires ATP
  3. glycolysis: 2.5 ATP/min, but lasts longer as glucose can be from blood or glycogen
  4. aerobic metabolism: 1 ATP/min, but lasts for extended time

39

passive tension

force generated bu stretching connective material of muscle tissue

does NOT require breakdown of ATP

force increases non-linearly with muscle stretch length

40

active tension

tension produced by the interaction of actin & myosin

increases to a maximum then decreases as stretch length increases

41

total tension

sum of passive & active tension at any given muscle length

42

optimal length

range of mescle stretch where active tension is at its maximum

43

factors influencing relationship between muscle stretch length & active tension change

  • relationship between stretched length & sarcomere length
    • small & large stretch lengths: overlap of thick & thin filaments doesn't favor myosin/actin interaction
  • stretch length affects ability of calcium to activate contractile proteins
    • increased length→ increased calcium effectiveness→ increase level of active force

44

contractile maximum force

isometrical muscle contraction

NO muscle shortening

shortening velocity is 0

afterload is too great for muscle to lift

45

what happens to muscle length & shortening velocity as afterload approaches 0?

maximum velocity (Vmax)

muscle is lifting itself

rate of shortening dependent solely on intrinsic ATPase activity

46

what is the relationship between action potential & muscle contraction duration?

AP= 1-2 milliseconds

muscle contraction 50x = 50-150ms

47

trepe

increase in active force development with increased stimultion (action potentials) frequency

48

tetany

aka tetanic contraction

sustained contraction due to very high frequencies of stimulation

49

pathological cause of tetany?

neurotoxin (tetanospasmin) released by Clostridium tetani (gram + anaerobic bacterium)

prevents release of inihibitory neurotransmitters (GABA & glycine)

50

what happens with recruitment of more motor units?

increase in active muscle force: summation

51

methods of calcium entry to smooth muscle cells

  1. voltage-gated channels
  2. ligand-gated channels: opened by neurotransmitter
  3. mechanical (strectch) sensitive channels: some, not all

52

where is calcium-induced calcium-release seen?

sarcoplasmic reticulum of smooth & cardiac muscle

53

how is calcium released from the sarcoplasmic reticulum of smooth muscle fibers?

calcium-induced calcium channels

& IP3 pathway

54

what is the major difference between skeletal/cardiac msucle & smooth muscle?

smooth muscle is regulated via thick filament regulation

55

thick filament regulation

altering of mysosin to regulate cross-bridge cycling of muscle contraction

via phosphorylation of myosin regulatory light chain→ activates causing actin binding

controlled by IP3/calmodulin pathway & myosin light chain kinase (MLCK) 

56

latch state

when myosin light chain is dephosphorylated while attached to actin

cross-bridging slows b/c myosin/actin bond attached longer

allows muscel to maintain tonic contraction w/less ATP requirement & at reduced calcium levels

57

what stops smooth muscle contraction?

myosin light chain phosphotase (MLCP) dephosphorylating myosin after detachment to actin

58

control mechanisms of smooth muscle contraction

  1. reduce Ca2+→ reduces reduces MLCK activity→ dephosphorylation prevails= muscle relaxation
  2. control of neurotransmitters that active cAMP pathway that leads to phosphorylated inactive MLCK
  3. increase activation of MLCP via hormone or nitric oxide
  4. PKC cascade→ increase of actin availability

59

relaxation in smooth muscle

Ca2+/H+-antiporters & Na+/Ca2+-antiporters

into sarcoplasmic reticulum & extracellularly

60

factors affecting contraction force of smooth muscles

spontaneous electrical activity of cell membrane

neurotransmitter release from autonomic nerves

hormones

"local" facotrs (pH, PO2, metabolites)

stretching & distention

61

smooth muscle differences of muscle force v. length relationship

broader active tension curve

greater passive tension at optimal length

Fmax comparable to skeletal muscle

62

Why is Vmax of smooth muscle much lower than in skeletal muscle?

slower myosin ATPase activity

mechanically very efficient→ lons sustained contractions

63

phasic smooth muscle

single unit

neighboring cells are conencted via gap junctions→ slow wave of contraction to spread from myocyte to myocyte

seen in ailmentary canal

64

tonic smooth muscle

multi unit

myocytes activated independently→ fine control

found in intrinsic eye muscles

65

3 division of ANS

  1. enteric nervous system
  2. sympathetic
  3. parasympathetic

66

structure of ENS

  • submucosal plexus
    • sits between luminal mucosa & circular muscle layers
    • senses luminal environment, regulates GI blood flow, & epithelial cell function
  • myenteric plexus
    • sits between circular & longitudinal muscle layers
    • digestive motility

67

What stimulates/activates ENS?

influened by parasympathetic & sympathetic fiber

but ENS functions autonomously via interneurons

68

what cells release acetylcholine?

cholinergic nerves

69

name for ANS cells that release norepinephrine

adrenergic nerves

70

what type of receptors bind acetylcholine?

nictotinic receptors: ligand-gated ion channels

muscarinic receptors: G protein-coupled receptors

71

what receptors bind adrenaline?

adrenaline= norepinephrine

alpha adrenoceptors

beta adrenoceptors

*both receptor types are G protein-coupled

72

where are nAChR found?

on both parasympathetic & sympathetic ganglionic (postsynaptic) neurons & adrenal medulla (sympathetic system)

73

where are mAChR found?

target tissues (parasympathetic)

& sweat glands (sympathetic)

74

what neurotransmitter does parasympathetic postganglionic neurons release to target cells?

ACh

75

what neurotransmitter does sympathetic postganglionic neurons release to target cells?

norepinephrine (NE)

or ACh only in the case of sweat gland stimulation

76

where are alpha adrenceptors found?

target cells of sympathetic autonomic nervous system

77

where are beta adrenceptors found?

on target cells of sympathetic autonomic nervous system

78

what is the function of Chromaffin cells? where are they found?

Chromaffin cells are in the adrenal medulla

responsible to the secretion of norepinephrine & epinephrine

79

neurotransmitter

released at nerve terminal

act on post-synaptic target

80

hormone

secreted into circulation

actions on target tissues distant from release site

81

structure & function of nAChR

2 alpha3 subunits & 3 beta4 subunits

ACh binding opens integral Na+channel→ depolarization of cell

82

mechanism of M1 class mAChR

M1, M3, M5

initial: activates Gq

→ activation of phospholipase C→ cleavage of PIP2 into DAG & IP3→ 2 IP3 bind ligand-gated Ca2+ channel in ER membrane→

final: increased intracellular Ca2+

83

mechanism of M2 class mAChR

M2 & M4

initial: activation of Gi

→ inihibition of adenylate cyclase (AC)→

final: decreased cAMP & acitvation of K+ channels (Gbeta/gamma unit)

84

mechanism of alpha1 adrenoceptor

initial: activates Gq

→ activation of phospholipase C→ cleavage of PIP2 into DAG & IP3→ 2 IP3 bind ligand-gated Ca2+ channel in ER membrane→

final: increased intracellular Ca2+

85

mechanism of alpha2 adrenoceptors

initial: activation of Gi

→ inihibition of adenylate cyclase (AC)→

final: decreased cAMP & acitvation of K+ channels (Gbeta/gamma unit)

86

mechanism of beta adrenoceptors

beta1, beta2, beta3

activates Gs→ activation of adenylyl cyclase→ increased cAMP

87

function of sympathetic autonomic nervous system

fight or flight

ex. increased hr, brochodilation, pupil dilation, promotes, ejaculation, GI vasoconstriction, GI inhibition

88

function of parasympathetic autonomic nervous system

rest & digest

ex. decreses hr, brochoconstriction, pupil constriction, GI activation, indirect promotion of erection

89

outline ANS regulation of eye

  • sympathetic innervation of alpha1 adrenoceptor→ contraction of dilator pupillae→ mydriasis (pupil dilation)
  • sympathetic innervation of beta adrenoceptor→ relaxation of ciliary muscle→ focus on far
  • parasympathetic innervation of M3 mAChR→
    • sphincter pupillae contraction→ miosis (pupil constriction)
    • ciliary muscle contraction→ focus on near

90

pilocarpine

  • target: mAChR
  • type of action: agonist
  • MOA: contraction of ciliary muscle→ reduces tension on trabecular meshwork→ opens trabecular meshwork pores→ faciliatates outflow of aqueous humor→ reduction of intraocular pressure
  • clinical use: topical ophthalmic for open-angle glaucoma

91

labetalol

  • target: alpha, beta1, & beta2 adrenoceptors
  • type of action: antagonist
  • clinical use: IV administration for HTN crisis
    • rapid effect, but short 1/2 life

92

propanalol

  • target: beta1 & beta2 adrenoceptors
  • type of action: antagonist
  • clinical use: HTN, cardiac arrhythmias, exertional angina

93

difference between mean body temperature & core body temperature

core temp is constant (37ºC)

skin temp is variable (24-35ºC), but average is 34ºC of naked person in neutral thermal environment

mean body temperature is the average of both

94

how does temperatur vary throughout the day?

w/circadian rhythm

lowest around 6am & highest around 6pm

deltaT= 0.5-1.0ºC

95

how does the menstrual cycle effect body temperature?

it slightly higher than normal by 0.2 degress post-ovulation & slightly lower during pre-ovulation

96

what amount of physical work is lost as heat?

75%

97

what are the mechanisms of heat production?

  • physical work (only 25% goes to the work itself)
    • maximum 12X basal metabolic rate (BMR)
  • internal work (organs)
  • thermoregulation: shivering→ muscle contraction for heat
    • max 5X BMR
  • nonshivering thermogenesis: fat burning
    • max 2-3X BMR

98

kilocalorie

amount of energy needed to increase the temperature of 1L of water by 1ºC

99

what are the heat dissipation mechanism?

  • conduction & convection
    • 20%
  • evaporation (aka sweat)
    • 50%
  • radiation: all warm surfaces radiate to cooler surfaces
    • 20% skin & 10% breathing

100

what is the goal of thermoregulation?

balance between heat production & heat dissipation

101

what is BMR?

1.2 kcal/min

increase of Tb by 1ºC for a 132lbs (60kg) person if heat weren't dissipated

102

how many kcal does it take to increase one kg of the body by 1ºC?

0.85kcal

b/c we are not just made of water

103

what is the maximal metabolic rate?

11kcal/min

for 60kg person, 1ºC/5minutes

104

difference between conduction & convection

conduction: heat loss at surface when surrounded by cooler static T

convection: heat loss at surface when surrounded by cooler moving T (breeze or flowing water)

105

what factors influence conduction & convection?

thickness & heat conductivity of insulating layer

usually air

our clothes work by trapping warm air close to our bodies

106

what factors influence the effectiveness of evaporation/sweating?

water vapor pressure of skin- water vapor pressure of ambience 

aka dependent on humidity of environment

107

how is heat dissipation decreased a low TA?

vasoconstriction & via use of arteriovenous shunts→ less blood flow to surface→ less heat dissipation

108

what non pathologic reason would cause hyperthermia at TA below 40ºC?

if the body is doing physical work

or if ambient humidity is above 70%

109

symptoms of hyperthemia

muscle cramping

edema

neuronal damage

starting at 42ºC

110

what hyperthermic temperture no longer supprts life?

44ºC

111

at what temperatures at 70% humidity is hypothermia seen?

TA= 5ºC

112

what does heat generation go up at very high ambient temperatures?

because sweating & sweat secretion require increased cardiac output

113

at what TA is skin profusion increased?

around 25-35ºC

114

at what TA does sweating begin?

around 35-40ºC

115

at what Tis shivering utilized for heat production?

5-25ºC

116

what is the cold center & why?

anterior hypothalamus

receives signal from peripheral warm receptors

inhibits heat generation & activates heat dissipation mechanism

117

what is the warm center & why?

caudal brainstem

receives signal from peripheral cold receptors

inhibits heat dissipation & activates heat generation mechanisms