1-cardio Flashcards

(82 cards)

1
Q

what is Ca2+ important for

A

contraction
excitation
secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what happens with high intracellular ca2+

A

cytotoxic (hypercontraction)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the concentration of cytosolic (intracellular) calcium

A

100nM (10^-7 M)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the concentration of extracelluar calcium

A

2mmolM (2.5^-3 M)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

where is calcium stored

A

ER and SR and mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are calcium sparks

A

localized release of intracellular calcium stores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are 5 calcium entry mechanisms

A

ligand gated,
voltage gated,
store operated calcium channels, GPCRs, and ryanodine receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

when do voltage gated ca channels open

A

when cell is depolarized

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are the types of voltage gated ca channels

A

LNPRT (Cav1=L, Cav2= NPR, cav3=T)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

where are N and P calcium channels and what do they do

A

neuronal and invovled in NT release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

where are L type calcium channels

A

heart and smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

name 3 voltage gated Ca2+ inhibitors

A

verpamil
diltiazem
dihydropyridines (nifedipine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does verapamil do

A

block voltage gated calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are dihydropyridines? give an example

A

type of voltage gated Ca2+ channel blocker
nifedipine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what does nifedipine do

A

type of dihydropyridines, blocks voltage gated Ca2+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is diltiazem?

A

inhibitor of voltage gated Ca2+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are verapamil, diltiazem and dihydropyridines (nifedipine) used for?

A

angina hypertension and some cardiac dysrhythmias by reducing contraction of vascular smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is an example of a highly permeable Ca ligand gated channel

A

NMDA glutamate channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what can be an issue with ligand gated channels

A

can cause so much Ca2+ entry the cell dies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what are ATP-gated P2X channels?

A

only true ligand gated ion channel in smooth muscle, very calcium permeable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what type of channel is the CRAC channel

A

store operated calcium channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what does CRAC channel stand for

A

calcium release activated channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how do SOC and CRAC increase intracellular store (mechanism)

A

Depletion of Ca(2+) from the ER causes STIM (calcium sensing proteins) to accumulate at ER-plasma membrane (PM)
-physical interactions allows CRAC channels to open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what are 3 calcium extrusion mechanisms

A

PMCA (plasma membrane calcium ATPase)
NCX sodium calcium exchanger
SERCA (sarcoplasmic endoplasmic reticulum calcium ATPase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
what does Ca2+ ATPase get energy from | why does it need energy
atp hydrolysis (transport across concentration gradients)
26
what does the plasma membrane PMCA pump do
keep cytoplasmic Ca2+ low by pumping it out of the cell (type of Ca2+ ATPase)
27
what does the SERCA pump do
keep cytoplasmic Ca2+ low by pumping it into ER or SR (type of ATPase)
28
what does thapsigargin do
block SERCA pump, can cause contraction due to increased intracellular calcium)
29
what does the NCX Na-Ca exchange do (which molecules how many and where)
brings 3 Na+ in and 1 Ca2+ out
30
how does NCX get energy
couples the flow of 3 Na+ ions down their EC into the cytosol to the move 1 Ca2+ ion out of the cell against its concentration gradient
31
where is the NCX
on plasma membrane
32
where is PMCA
on plasma membrane
33
why can NCX cause depolarization?
the transporter is elecrogenic (it causes the net movement of 1 positive charge inward, since it moves 3 Na+ in and 1 Ca2+ out)
34
describe reverse mode NCX activity
caused by a reduction in the Na+ concentration gradient if the concentration of Na+ in the cell is too high, it will action case Na+ to leave the cell and bring Ca2+ in
35
what are 2 transporters that do exchange between ER SR and cytosol
inositol tris phosphate receptor (GPCR) ryanodine receptor (calcium induced calcium release)
36
what does the IP3 receptor do
ligand gated ion channel in the SR/ER that is activated by IP3 results in activation of Gq signalling and elevation of intracellular calcium (and DAG --> PKC)
37
what does RYANODINE do
activates RyR at low concentrations (nanomolar) but closes them at high concentrations (micromolar)
38
what kind of ryanodine receptor is involved in skeletal muscle contractions
RyR1
39
what kind of ryanodine receptor is involved in cardiac muscle contractions
RyR2
40
what does ryanodine receptors do to ca2+ release in cardiac muscle? mechanism?
CICR (calcium induced calcium release) Ca2+ acts on RyR to release Ca2+ from the ER/SR
41
what does CAFFEINE do?
sensitizes ryanodine receptor and causes Ca2+ release from ER SR at physiological Ca2+ concentrations sensitizes muscle to contract more stimulant
42
what does dantrolene do | what is it similar to
blocks RyR (like ryanodine does at high conc)
43
what is dantrolene used for
malignant hyperthermia caused by genetic RyR abnomalities or anesthesia mutations cause RyR to be oversensitive, resulting in too much intracellular calcium, too much heat release and hyperthermia
44
what is calmodulin
ca binding protein that activates many effectors
45
what is the main downstream effector for calmodulin
CaM kindase | calcium calmodulin kinase
46
what are some molecular targets for ca
``` enzymes kinases phosphatases transcription factors synaptic vesicle proteins (NT release) contractile proteins ca binding proteins as intermediate ca sensitive ion channels ```
47
Is na higher on inside or outside
outside
48
Is k higher on inside or outside
inside
49
Is Cl higher on inside or outside
varies, but higher outside
50
what determines resting membrane potential
resting K channels (selectively K permeable)
51
what is the normal resting membrane potential determined by K+
-40 to -80 mV
52
which three ion pumps are primarily responsible for controlling ion concentrations within the cell?
NaK ATPase and Ca ATPase and NCX)
53
does Na K pump cause hypo or hyper polarization and why
hyperpolarization because it makes the inside more negative (3 na out 2 k in)
54
what does digoxin do and what is its drug class
digitalis cardiac glycosides, blocks Na K ATPase
55
what happens in action potential (2 main things)
threshold stimulus causes opening of voltage gated Na+ channels, rapid influx of Na+, followed by inactivation of Na+ channels and delayed outward flux of K+ results in repolarization
56
what causes the refractory period
inactivation of Na channels
57
is the AP and depolarization mechanism same in all tissues
no, varies per tissue. complex in heart
58
what do drugs that cause depolarization do to excitability
increase
59
what do drugs that cause hyperpolarization do to excitability
decrease
60
what does a stronger depolarizing stimulus do to AP
increases # of them
61
what is the classical pharmacology method of seeing drug effects of muscle contraction
take contractile tissue and put into organ bath add drug monitor contractions with transducer
62
what causes contraction of muscle
interaction between actin and myosin fueled by ATP and initiated by increase in intracellular Ca interaction is inhibited, by troponin, MLCK
63
what does ACh at nAChR do
causes depolarization (excitatory junction potential)
64
decribe the steps of skeletal muscle contraction
ACh activated nAChRs, resulting in depolarization AP propogates thru T-tubules, activating L-Type Ca2+ channels (aka dyhydropyridine receptors) Mechanical stimulation of RyR1 receptors on the ER/SR, causing Ca2+ release Ca2+ release binds troponin, removing it from myosin binding site on actin Muscle contraction!
65
what happens when L-type dihydropyridine ca receptors are activated in skeletal muscle
RyR1 receptors on adjacent ER/SRcome close to L-type dihydropyridine ca receptors to activate Ca release
66
what 2 receptors need to be together to cause ca release in skeletal muscle
L-type dihydropyridine ca receptors and RyR1
67
what happens in skeletal muscle once ca is release
ca binds to troponin
68
what does troponin do
stops interaction between actin and myosin
69
what happens when ca binds to troponin
stops troponin blocking interaction by actin and myosin so that you can have contraction
70
what kind of tissue is myogenic and what does it mean
heart because it does not need stimulus to start contraction
71
describe cardiac muscle contraction
Change in voltage results in opening of L-type Ca2+ channels Ca2+ causes activation of Ryr2 to release Ca2+ from the ER/SR CICR Contraction!
72
what receptor in heart is activated by AP
L-type Ca2+ receptors (voltage gated)
73
what happens when L-type ca receptors are activated in heart (2 things)
releases ca | and that ca activates RyR2 to release ca from ER SR
74
describe the difference between skeletal and cardiac muscle contraction
skeletal needs L type and ryanodine to be beside each other heart doesn't (L type releases calcium which stimulates RyR)
75
what makes smooth muscle contraction different than heart and skeletal
no troponin!!!
76
if smooth muscle lacks troponin, what causes contraction?
myosin light chain kinase
77
what do agonists working through Gq do to smooth muscle
contract (alpha 1)
78
what do agonists working through Gs do to smooth muscle
relax (beta 2)
79
what does NO do to smooth muscle
relax (guanylyl cyclase)
80
what does cAMP do in the smooth muscle contraction pathway and how?
inactivate MLCK by phosphorylating it (double phosphorylation) INHIBITS CONTRACTION/CAUSES RELAXATION
81
what does cGMP do to smooth muscle pathway contraction pathway and how?
dephosphorylating myosin-LC-PO4 INHIBITS CONTRACTION/CAUSES RELAXATION
82
what does Gq signalling do to smooth muscle contraction and how?
intracellular Ca2+ release --> activated Ca2+ calamodulin --> activate MLCK --> phosphorylated myosin-LC --> contraction