6.4-6.10 Flashcards
describe the charge difference inside the membrane compared to the outside
inside slightly negatively charged compared to outside
what is the electrochemical gradient composed of
charge difference and concentration differences across a membrane
what is the electrochemical gradient maintained by
channels and carrier proteins
when does a membrane potential exist
when there is an electrochemical gradient
what does a membrane potential require
- ion concentration difference across membrane resulting in charge separation
- membrane which is selective permeable for at least one of ionic species
which ions the major contributors to membrane potential in animal cells
- K+, Na+, Cl-
which ions don’t necessarily contribute to membrane potential
Ca2+ and Mg2+
what 2 components are important for maintaining resting membrane potential
- K+ leak channels
- Na+/K+-ATPase
are K+ leaky channels open or closed at resting membrane potential
open
K+ leaky channels
allows K+ ions out of the cell and down their electrochemical gradient
- make inside more negative
what does the Na+/K+-ATPase pump
- 2 K+ in
- 3 Na+ out
functions of Na+/K+-ATPase pump
- make inside more negative
- helps increase K+ gradient so K+ leaky channels can still keep working
what would happen if the Na+/K+-ATPase pump didn’t work
concentrations of K+ and Na+ would be the same on both sides of the membrane
membrane potential changes according to which ions have the most ________ _____________ at a time
open channels
depolarization
occurs when Na+/Ca2+ channels open
- ions flow into cell, making membrane potential more positive
repolarization (and hyperpolarization)
when K+ channels open, K+ moves out of cell, membrane potential becomes more negative
what do K+ channels form
narrow, water-filled pore
are K+ channels more selective for K+ or Na+
highly selective for K+
- Na+ 10^4 times less likely than K+ to permeate K+ channels
K+ channels are ____________
tetramers
each identical subunit of a K+ channel contributes to what?
a central pore
2 common types of alpha subunits
- 2TM/1P
- 6TM/1P
what does TM stand for
transmembrane
what does P stand for
pore loop
2 main parts to a (K+) channel
selectivity filter and central cavity
purpose of central cavity in K+ channels
stabilizes K+ ions before they go through
purpose of selectivity filter in K+ channels
dehydrates the ions in order for them to pass through
how do selectivity filters dehydrate ions
- partial negative charge of oxygen (carbonyl) atoms acts as surrogate water molecules
- lowers dehydration energy for permeating K+ ions
other ions (Na+) have the wrong size ________ _______ to fit through K+ channels in a way that dehydration would be energetically favorable
hydration shells
speed of K+ channels
- 10^8 ions/second
- each ion partially dehydrates, passed through filter, and rehydrated in 10 nsec
does a straight or bent conformation of alpha helices in the K+ channel mean it is closed
straight
3 subfamilies of K+ channels
- gates sensitive to metabolic state of the cell
- gates sensitive to ligand binding
- gates sensitive to voltage
where do ligands bind in a K+ channel
to the intracellular C-terminal domain
ex. of ligands
Ca2+, ATP, trimeric G proteins, polyamines
ex. of K+ gates gated by both ligand and voltage
BK channels (big K+)
specifics of BK channel
- S1-S4 VSD
- RCK1-RCK2 - Ca2+ binds + depolarization
- opens channels
- hyperpolarization
- closes other channels
ex. of K+ channels
- Ca2+-activated K+ channel (dual ligand)
- voltage-gated K+ channel (resting potential)
how do voltage-gated channels sense changes of membrane electric fields
via several positively charged aa residues in voltage-sensing domain of transmembrane domain
- controls opening/closing of pore
how are voltage-dependent Na+ channels activated
by membrane depolarization
3 classes of Na+ dependent membrane proteins
- voltage
- epithelial
- Na+/substrate transporters
what do voltage-dependent Na+ channels require
electrochemical Na+ gradient generated by Na+/K+-ATPase
IMPS
voltage-gated Na+ channel
what are IMPS formed with
single pore-forming subunit
what happens during depolarization
Na+ channels open, Na+ ions flow into the cell down their gradient, channel closes within milliseconds and Na+ influx stops
2 steps of Na+ inactivation
- fast (quickly reversed during repolarization)
- slow
when does voltage-dependent inactivation of Na+ channels occur
very quickly after activation
what does the selectivity filter of Na+ channels bind to
tetrodotoxin
where is tetrodotoxin from
puffer fish
what does tetrodotoxin cause
paralysis by inactivating voltage-gated Na+ channels involved in initiation/propagation of action potentials in nerve cells
is the closed Na+ structure symmetric or asymmetric
asymmetric
Na+ channels are targets for what?
- local anesthetics
- drugs used to treat cardiac arrhythmias
drugs used to treat cardiac arrhythmias
class I anti-arrhythmic drugs that seem to bind on the intracellular side of the Na+ channel and inhibit membrane depolarization
ENaCs
epithelial Na+ channels
what are ENaCs primarily regulated by
hormones
true or false: ENaCs are rapidly inactivated
false
where were ENaCs first found
epithelial cells
where else are ENaCs found
many other cell types - like neuronal
function of ENaCs
mediate bulk flow of Na+ ions, influence water transport across cell layers
what does the function of ENaCs depend on
Na+ gradient established by the Na+/K+-ATPase
where are ENaCs located in epithelial cells
apical membrane
what regions are ENaCs located in (kidneys)
epithelial cells of distal tubule and collecting ducts of each kidney nephron
how do ENaCs function in kidneys
allow Na+ ions from filtrate to enter cells down their gradient, Na+/K+-ATPase helps by removing Na+ from epithelial cell and transporting it back into the blood capillary
how does Na+ transport affect K+ in kidneys
creates electronegative environment, which favors K+ secretion into filtrate through apical channels
reabsorption of Na+ is regulated by __________ and _____________
aldosterone, vasopression
where is aldosterone from
adrenal glands
where is vasopressin from
pituitary gland
where does aldosterone and vasopressin bind
receptors on kidney cells
result of binding of aldosterone and vasopressin
- reabsorb Na+
- retain water
- increase blood pressure
diuretic drug that blocks Na+ reabsorption
amiloride
how does amiloride block Na+ reabsorption
competes with Na+ ions
result of amiloride blocking Na+ reabsorption
- decreased Na+ reabsorption
- lower Na+ concentration in blood
- lower blood pressure
where are Ca2+ concentrations high
in extracellular fluid, ER, SR
- 10^4 times lower in cytoplasm for resting cells
several different Ca2+ channels on the PM, ER, and SR catalyze selective transport of what?
Ca2+ ions down electrochemical gradient into the cytosol
what are Ca2+ channels gated by
- ligands
- voltage changes
- Ca2+ itself
influx of Ca2+ increases intracellular Ca2+ that triggers responses such as
- muscle contraction
- hormone or neurotransmitter release
- activation of Ca2+-dep signaling cascades
- gene transcription
what can function as a cytoplasmic Ca2+ sensor
CaM
why are Ca2+ channels highly selective
due to selectivity filters
what do the amino acid residues for Ca2+ selectivity filters have instead of carbonyl O?
carboxylate O
- glutamate residues form EEEE locus
permeation rate of Ca2+ channels
10^6 per second
do K+ channels or Ca2+ channels have a higher permeation rate
K+
in vitro vs. in vivo
vitro: experiments outside living org.
vivo: living org.
functions of Cl- channels
- cell volume
- ionic homeostasis
in vitro Cl- channel function as
nonselective anion channels
- can conduct other anions
in vivo Cl- channel function
Cl- most abundant anion predominant ion transported by these channels
for Cl- channels, ______ __________ and __________ are intrinsically coupled
ion conductance, gating
Cl- channels have _________-charged regions pointing into the __________
positively, center plane of the membrane
3 different gene families of Cl- channels
- CLC gene family
- cystic fibrosis transmembrane conductance regulator
- ligand-gated (y-aminobutyric acid (GABA) receptor and glycine receptor family)
CLC gene family
- targeted to PM or intracellular compartment membranes
- some transport Cl- in exchange for protons
cystic fibrosis transmembrane conductance regulator
only member of family of ATP-binding cassette (ABC)
ligand gated (y-aminbutyric acid (GABA) receptor and glycine receptor family
functions in nervous system
