CH 13 Membrane Channels and Pumps P2 Flashcards
K+ Channel
four subunits - homologous to one of repeated units in Na+ channel.
cone-shaped.
Na+ Channel Purification
on basis of affinity to neurotoxin tetrodotoxin
Na+ Channel
4 repeated regions of similar seq.
each region has 5 hydrophobic segments, 1 hydrophilic segment.
Ca+ Channel
homologous to Na+ channel
Shaker
mutated version of K+ channel
K+ Channel reveals the basis of?
ion specificity
The K+ channel transports K+ across the membrane ____ and ____.
selectively
rapidly
K+ Channel does not transport?
larger ions - too big to enter channel.
smaller ions - cannot interact w/ selectivity filter.
What happens to the K+ ion in the K+ Channel?
Selectivity filter has 4 binding sites.
Hydrated K+ ions enter sites, 1 at a time, losing hydration shells.
when 2 ions occupy adj. sites - electrostatic repulsion forces them apart.
ions enter channel from one side, other ions pushed out other side.
These 2 channels are homologous to the K+ Channel:
Na+ and Ca2+
Ca2+ Channels have what 4 residues?
(4) E - glutamate
Na+ Channels has what 4 residues?
D - aspartate
E - glutamate
K - lysine
A - alanine
K+ Channel Structure
4 ion-binding sites
accounts for rapid transport of K+ ions down [gradient]
Voltage Gating Channels
Na+ and K+ Channels.
change conf. w/ change in membrane potential.
Which segments of the K+ channel are involved w/ voltage gating?
S1 - S4 - paddle domains.
-changes in membrane potential alter paddle conf. to open / close channel.
S4 - voltage sensor.
How is the K+ inactivated?
physically blocking channel.
ball segment of channel tethered by polypeptide segment (chain).
A channel can be inactivated by?
occlusion of pore
Mutants that do not inactivate lack?
ball and chain
Protease-Accessible
protease can be used to cleave chain provided chain is flexible.
Depolarization opens?
channel.
creates binding site for ball, inactivates channel.
Acetylcholine Receptor
ligand-activated channel tat acetylcholine binds to.
NT released into synaptic cleft.
opens channel for K+ and Na+.
triggers action potential.
Acetylcholine Receptor Subnunits
4 w/ stoichiometry α2βγδ arranged in pentameric ring
Acetylcholine binding causes?
conf. changes - rotate membrane-spanning helices so pore opens.
Na+ and K+ ions pass through.
Equilibrium Potential
membrane potential.
equilibrium est’d.
driving force of [gradient] countered by charge repulsion (like charges).
Equilibrium Potential: Nerst Eqn
Veq = −(RT/zF) ln([X]in/[X]out)
R: gas constant
F: Faraday constant
z: ion charge
If ion X+ is unequally distributed across a membrane it will?
tend to move down [gradient].
movement inhibited by accumulation of + charges.
In the absence of stimulation the resting potential for a typical neuron is?
-60 mV.
close to potential for K+ bc small # K+ channels open.
Action Potential (APs)
- acetylcholine receptor activated, K+ flows out, Na+ flows in.
- membrane potential changes, Na+ channels activated.
- voltage-gated K+ channels open.
ball of Na+ inactivates Na+ channel. - K+ open - membrane potential drops to K+ equilibrium potential.
- ball closes K+ channel.
membrane potential to initial state. - propagates down nerve membrane as action potential.
LQTS: Long QT Syndrome
recovery of action potential delayed.
loss of consciousness, heart arrhythmia, sudden death.
QT
feature of electrical activity pattern measured by electrocardiography
Most common mutation of LQTS:
inactivate K+ channels
prevent proper trafficking of channels to plasma membrane.
The loss of K+ permeability _____.
slows repolarization of membrane, delays heart contraction.
Gap Junctions
cell-to-cell channels
allow ions, small molecules to flow btw communicating cells.
intercellular communication
What molecules can pass through gap junctions?
polar molecules w/ mass < 1kDa
A cell-to-cell (gap) junction is composed of?
12 molecules of connexin
Connexon / Hemichannel
6 hexagonally arranged connexins form this half-channel
Connexons from ____ form ____.
adjacent cells
a gap junction
Gap junctions traverse ____ to allow ____.
2 membranes
cytoplasm-to-cytoplasm communication.
Cardiac Muscle Structure
elongated branching cells
1-2 centrally located nuclei
Cardiac Muscle contains which filaments?
actin and myosin
Intercalated Discs
in cardiac muscle specialized cell-cell contacts. cell membranes interdigitate. desmosomes. gap junctions.
Intercalated Discs: Desmosomes
hold cells together
Intercalated Discs: Gap Junctions
allow action potentials to move from one cell to next
In cardiac muscle, electrically, these behave as a single unit:
atria and ventricles
Aquaporins
allow rapid, specific movement of water across membranes.
hydrophilic residues that line water channel.
What prevents the transport of protons through aquaporins?
specific positively charged residues toward center of channel
The heart uses coordinated changes in ____ to create efficient muscular contractions that allow effective ____.
membrane potential.
pumping of blood throughout body.
How can the heart beat spontaneously w/o input from the rest of the body?
pacemakers
Pacemakers
unusual capacity for mixed Na+/K+ conductance when membranes are hyperpolarized
Funny Current
membrane permeability of pacemakers
Pacemakers make up the?
SA Node
SA Node Cells
spontaneously gen ~100 action potentials / second
SA Node
sinoatrial node.
most important region.
where action potentials are gen’d.
Conducting System
- APs from SA Node to AV (atrioventricular) node.
- Aps AV node along AC bundle.
- AV bundle to right and left bundle branches.
Aps to apex of each ventricle along bundle branches. - APs carried by Purkinje fibers from bundle branches to ventricular walls and papillary muscles.
Heart Valve Function: Blood Flow into Left Ventricle
bicuspid valve open.
valve cusps pushed by blood into ventricle.
aortic semilunar valve overlap as pushed by blood in aorta toward vessicle.
Heart Valve Function: Blood Flow out of Left Ventricle
bicuspid valve closed.
cusps of valves overlap as pushed by blood toward left atrium.
aortic semilunar valve open.
cusps of valve pushed by blood toward aorta.
The current is ___ during the action potential.
off
The current is ___ when the membrane returns to its ___.
on.
resting potential.
The current is only active at ____, leading to a gradual ____ to a level that ____.
rest.
depolarization of the membrane.
triggers initiation of an AP.
HCN Hyperpolarization-activated Cyclic Nucleotide-gated Channels
responsible for funny current.
HCN4 isomer highly expressed in SA node.
The HCN Channels are opened by?
hyperpolarization
The HCN Channels close when?
membrane is depolarized.
Sick Sinus Syndrome
mutations in HCN4.
fewer HCN4 channels open at resting potential, slower depolarization.
Sick Sinus Syndrome Symptoms:
abnormally low heart rate.
fainting.
fatigue.
What is req’d to open the mutant HCN4 receptor?
greater hyperpolarization
