1-cardio Flashcards
what is Ca2+ important for
contraction
excitation
secretion
what happens with high intracellular ca
toxic
what is free intracellular calcium levels at usually (#)
100nM (10^-7 M) (0,1 micro molar)
what is extracellular calcium levels at usually (#)
2mmolM (2.5^-3 M)
where is calcium stored
ER and SR and mitochondria
what are calcium sparks
localized release of calcium
what are 3 calcium entry mechanisms
ligand gated,
voltage gated,
store operated calcium channels
when do voltage gated ca channels open
when cell is depolarized
what are the types of voltage gated ca channels
LNPRT (Cav1=L, Cav2= NPR, cav3=T)
where are N and P calcium channels and what do they do
neuronal so invovled in NT release
where are L type calcium channels
heart and smooth muscle
what does verapamil do
block L type calcium channels
what are dihydropyridines and what is a type of one
class of drug nifedipine
what does nifedipine do
block L type calcium channels
what do dihydropyridines do
block L type calcium channels
what are dihydropyridines (nifedipine) and verapamil used for
angina hypertension and some cardiac dysrhythmias
when are ligand gated channels activated and what does it cause
when NT or other agonists cause Ca influx
what is an example of a highly permeable Ca ligand gated channel
NMDA glutamate channels
what can be an issue with ligand gated channels
too much ca entry can kill (like too much glu excites them to death)
what are ATP-gated P2X channels and whats the big deal with them
only true ligand gated ion channel in smooth muscle
-highly ca permeable
what type of channel is the CRAC channel
store operated calcium channel
what does CRAC channel stand for
ca release activated Ca
when do SOC and CRAC channels dp
allow ca entry when intracellular stores are depleted (ER SR)
how do SOC and CRAC increase intracellular store (mechanism)
STIM1 accumulates where ER is juxtaposed to the plasma membrane
-physical interactions allows CRAC channels to open
what are 3 calcium extrusion mechanisms
PMCA-plasma membrane NCX-calcium ATPase
sodium calcium exchange
SERCA sarcoplasmic endoplasmic reticulum calcium ATPase
what is the main role of calcium extrusion mechanisms
keep ca in cell low by pumping it into ER or out of cell
what does ca atpase get energy from
why does it need energy
atp hydrolysis (transport across concentration gradients)
what does the plasma membrane PMCA pump do
keep cytoplasmic ca low by pumping it out of the cell
what do PMCA pumps require
energy from ATP hydrolysis
what does the SERCA pump do
keep cytoplasmic ca low by pumping it into ER or SR
what does thapsigargin do
block SERCA pump
what does the NCX Na-Ca exchange do (which molecules how many and where)
brings 3 na in and 1 ca out
how does NCX get energy
uses the Na gradient to get energy (brings na inside like its gradient wants it to) to get ca out
where is the NCX
on plasma membrane
where is PMCA
on plasma membrane
what kind of exchanger is NCX (special word we learned)
electrogenic because it causes depolarization by net inward movement of positive charge
what transporter is involved in generating AP in many regions of heart
NCX
what transporter is electrogenic
NCX
and NaK ATPase
how does a reduced na gradient affect intracellular Ca2+ and why
accumulation inside because it needs the gradient to let it leave
what are 2 transporters that do exchange between ER SR and cytosol
inositol tris phosphate receptors (IP3R) ryanodine receptor (RyR)
what does the IP3 receptor do
activates ca release from SR ER
what kind of channel is IP3 receptor
ligand gated
where is the ip3 receptor
ER SR
what kind of mechanism causes ip3 to elevate ca
Gq
what activates inositol trisphopshate receptor
IP3
what does RYANODINE do
activates RyR at low concentrations (nanomolar) but closes them at high concentrations (micromolar)
what kind of ryanodine receptor is involved in skeletal muscle contractions
RyR1
what kind of ryanodine receptor is involved in cardiac muscle contractions
RyR2
what does ryanodine receptors do to ca release
increase - ca induced ca release from ER SR
what kind of receptor causes ca induced ca release
ryanodine receptor
what does CAFFEINE do to what receptor
sensitizes ryanodine receptor and causes ca release from ER SR at physiological ca concentrations
what does dantrolene do
what is it similar to
blocks RyR (like ryanodine does at high conc)
what is dantrolene used for
malignant hyperthermia (happens in surgery) due to genetic RyR abnomalities
what is calmodulin
ca binding protein that activates many effectors
what are 2 protein characteristics for calmodulin
dimer
4 ER hand binding domains for ca
what is the main downstream effector for calmodulin
CaM kindase
calcium calmodulin kinase
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
Is na higher on inside or outside
outside
Is k higher on inside or outside
inside
Is ca higher on inside or outside
outisde (very low inside)
Is Cl higher on inside or outside
varies, but higher outside
what determines resting membrane potential
resting K channels (selectively K permeable)
what is the normal resting membrane potential determined by K+
-40 to -80 mV
what causes ionic concentrations to be set
ion pumps (NaK ATPase and Ca ATPase and NCX)
how many na and k pumped and where in NaK ATPase
2 K in
3 Na out
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)
what does digoxin do and what is its drug class
digitalis cardiac glycosides, blocks Na K ATPase
is Na K Atpase electrogenic
yes
what is Na concentration inside and outside
inside 12mmol
ouside 145mmol
what is K concentration inside and outside
150 inside
2.4 outside
what is Ca concentration inside and outside
0.1 micro inside
2mmol outside
what is Cl concentration inside and outside
5mmol inside
125mmol outside
what happens in action potential (2 main things)
depolarization causes opening of Na+ channels to bring Na+ inside
then slower outward K+ flux to end AP
what causes the refractory period
inactivation of Na channels
is the AP and depolarization mechanism same in all tissues
no, varies per tissue. complex in heart
what do drugs that cause depolarization do to excitability
increase
what do drugs that cause hyperpolarization do to excitability
decrease
what does a stronger depolarizing stimulus do to AP
increases # of them
what is the classical pharmacology method to seeing drug effects of muscle contraction
take contractile tissue and put into organ bath
add drug
monitor contractions with transducer
what causes contraction of muscle
interaction between actin and myosin fueled by ATP and initiated by increase in intracellular Ca
what does ACh at nAChR do
causes depolarization (excitatory junction potential)
what happens when excitatory junction potential reaches threshold
generates muscle AP (open Na+ channels)
What kind of receptor in skeletal muscle is activated by voltage
L-type dihydropyridine ca receptors
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
what 2 receptors need to be together to cause ca release in skeletal muscle
L-type dihydropyridine ca receptors and RyR1
what happens in skeletal muscle once ca is releasd
ca binds to troponin
what does troponin do
stops interaction between actin and myosin
what happens when ca binds to troponin
stops troponin blocking interaction by actin and myosin so that you can have contraction
what kind of tissue is myogenic and what does it mean
heart because it does not need stimulus to start contraction
what receptor in heart is activated by AP
L-type ca receptors
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
what is different with skeletal and cardiac muscle contraction
skeletal needs l type and ryanodine to be beside eachother heart doesnt (2 type releases calcium which stimulates ryan)
does RyR2 and L type need to touch to release ca in heart
no
ca from L type stimulates RyR2
what makes smooth muscle contraction different than heart and skeletal
no troponin!!!
what causes contraction in smooth muscle- what is the main thing
myosin light chain kinase
what do agonists working through Gq do to smooth muscle
contract (alpha 1)
what do agonists working through Gs do to smooth muscle
relax (beta 2)
what does NO do to smooth muscle
relax (guanylyl cyclase)
what does cAMP do in the smooth muscle pathway and how
inactivate MLCK by phosphorylating it
INHIBIT CONTRACTION
what does cGMP do to smooth muscle pathway and how
dephosphorylating myosin LC PO4
INHIBIT CONTRACTION
