Lecture 19 - Txpt II Flashcards
Compare ion channel speed to ion pump speed
Channel 1000x > than pump
The opening and closing of ion channels are responsible/shape the membrane _____.
Potential (flow down [gradient] changes electrical potential)
Voltage gated ion channels respond to _____.
changes to membrane potential
Chemically/ligand gated channels respond to _______.
ligands (or “signals”) binding to them.
Mechanically gated channels respond to _____.
mechanical forces that deform them (P, Temp, pain, etc).
Describe the “patch clamp” method of channel isolation.
A small (1 micron) pipette is placed against a cell’s plasma membrane. Depending on the amount of suction applied, either the entire cell (low suction) is removed, or just a portion of the membrane with embedded channels is torn away (high suction).
Explain how homology of a protein sequence across species indicates the importance of said protein.
If a protein is homologous, it is a highly conserved protein, and therefore highly important to cell function. There is homology among sodium channels, potassium channels, etc.
Describe the mechanism of “-caine” anesthetics.
Transmembrane (“TM”) domains 5-6 act as a pore when activated by voltage sensing domain 4 on the Na+ channel. Though the Na+ channel may be activated, -caine anesthetics block the pore formed by TM5-TM6
Tetrodotoxin acts as a (permanent/transient) blocker of Na+ channels.
permanent
K+ channels are comprised of 6 transmembrane domains (S1-S6). Which act as a voltage sensor, and which form the K+ channel pore?
S1-S4: voltage sensor
S5-6
Explain the K+ selectivity filter’s “Mechanism of Action.”
K+ is solvated in ICF. The large (10Angstrom) K+ channel pore will allow solvated K+ to enter. However, as the solvated K+ approaches the extracellular leaflet, the width decreases to 3 angstroms. The K+ is desolvated by the carbonyl groups there, and each subsequent positive, desolvated K+ is “repelled” out of the channel.
DRAW OUT!!!
What is the AA sequence for the K+ selectivity filter
TVGYG
Explain the Gibbs free energy basis for ion conductance through a K+ channel and how it affects selectivity.
To pass through a K+ channel, ions must be desolvated, then resolvated once through the channel.
For K+, the total change in E* for desolvation/solvation via the K+ channel is (-), or favorable.
For Na+, the total change in E* for desolvation/solvation via the K+ channel is (+), or unfavorable.
Voltage gated channels change formation due to _____
changes in membrane potential.
Inactivation of a voltage gated channel occurs through an “inactivation domain.” What end of the channel protein is this located (C-term/N-term)?
C-terminus
Describe the steps of voltage gate inactivation:
1) An action potential (depolarization) opens the channel
2) Eventually, hyperpolarization moves the ball into the intracellular portion of the pore opening
Describe the structure of the ACH-R
2xα; β; γ; δ
Differing [Na+] and [K+] are generated by _____.
Na+/K+/ATPase pumps in the plasma membrane
Outline the steps of an action potential
1) Transient changes in membrane potential reach a threshold
2) Conductance of Na+ rises by opening of v-gated Na+ channels secondary to the S4 “switch” domain
3) Depolarization occurs by Na+ flowing through S5-S6 pores
4) At +35mV, Na+ inactivation gate closes, and K+ channel opens
5) K+ efflux hyperpolarizes the cell
6) At -90mV (appx.) the K+ inactivation gate closes and hyperpolarization stops
7) Na/K/ATPase pumps return cell to RMP
Explain the transmission of an action potential at the NMJ.
1) An action potential reaches the telodendria
2) Depolarization opens voltage gated-Ca2+ cells
3) Calcium enters the cell and causes fusion of vesicle PM/telodendria PM (SNAP protein)
4) Exocytosis of NT
5) Binds to receptor
6) Opening of ligand-gated channels on post-synpatic tissue causes Na+/K+ movement (Na+ influx > K+ efflux)
7) If depolarization is large enough, end plate potential produced (is this just in muscle?)
8) PMCA removes Ca2+ from telodendria (Ca2+ is cytotoxic)
“Cell to cell” channels important to action potential/cell communcation.
Gap junctions
Describe structure of gap junctions
One channel is comprised of 12 connexins. 6 connexins make 1 connexon. 2 connexons make one f(x) channel.*
*1 connexon on one cell, 1 connexon on the other
Explain the selectivity of gap junctions
Gap junctions are
Explain why connexons are important in tissue like the lens of the eye and bones.
These tissues lack abundant vasculature. Therefore, gap junctions provide a means of nourishment.
What closes gap junctions?
High [Ca2+] and [H+]. These molecules are cytotoxic/inducers of apoptosis.
How are connexons regulated
Hormone induced phosphorylation/membrane potential changes
Describe how a gap junction is different from an ion channel.
Ion channel: Spams 1 PM ICF to ECF connection Synthesized by 1 cell Rapid open/close
Gap: Spans 2 PM Cytosol to cytosol connection Synthesized by 2 cells Open for seconds/minutes
Aquaporins are found in RBCs, kidneys, and corneas. Why?
These tissues require large amounts of water to be extruded past cell membranes.
Describe the structure of aquaporins.
6 transmembrane spanning alpha domains
Transport channels are responsible for ______ transport.
facilitated, passive
What molecules are gap junctions permeable to?
A. Proteins, polysaccharides, and nucleic acids
B. Large, hydrophillic (> 1kDa) molecules
C. Small hydrophillic (
C. Small hydrophillic molecules
