[2] Class 4: Transport Through Membrane 2 Flashcards
Integral, polytopic membrane proteins
400 genes in human genome
Mediates Facilitated passive transport
Highly selective and specific for ions
1000X faster than pumps
Opening and closing channels shapes membrane potential
Ion channels
Why are transport ions 1000x faster than pumps?
They have efficient gates that can be voltage gated and not require the sequential steps of waiting for ATP binding and hydrolysis for the action to occur.
3 types of ion channels:
Voltage
Ligand
Mechanical
Respond to change in membrane potential
Voltage-gated
Respond to ligand such as neurotransmitters
Chemically gated
Respond to mechanical stimuli, detect vibration, pressure. Stretch, touch, sounds, tastes, smell, heat, volume, and vision. Found in sensory neurons:
Mechanically gated
How was ion channeling proven by experiment?
Patch clamping
Who was involved in first patch clamping experiment?
Erwin neher and Bert Sakmann
How long are ion channels open?
Msec ‘s
Current applied to patch clamping
4 pA
S5 and S6 form:
The pore of the ion channel
S1-S4 form the:
Voltage sensor
Sequence homology:
Sodium, Ca+, K+ all homologous seem to be handed down in evo.
Model organism for Na+ channel testing:
Electric eel
260 kDa protein
4 terminal repeats
6 transmembrane domains
TM 4-voltage sensor
Na+ channel
What is the basis of topical anesthetics:
Block sodium channels
Toxic substance from pufferfish that acts to inhibit Na+ channels:
Tetrodotoxin
Voltage sensor for K + channel
S1-s4
S5-s6 K+ channel:
Pore
Who determined structure of K+ channel and when?
Robert mackinnon; 1998
K+ direction of movement in tissue:
Move from inside out
HOw does selectivity filter work for K+ channel?
Hydrated K+ dehydrated when going through selectivity filter. Carbonyl bonds are forms w/ AA’s in channel. Rehydrated exiting channel.
What is the signature of potassium channel?
TVGYG
Which is larger? Na+ or K+
Na+ = 0.95 å
K is 1.33å
Why cant Na+ pass through K+ channel if it is smaller than K+?
Na+ is rejected b/c of higher energetic cost of dehydrating sodium would not be recovered when passing through channel.
K+ resolvation energy > desolvation energy
How many binding sites for K+ channel?
4
Describe the fundamental reason that K+ ions continue through channel as opposed to remaining bonded to carbonyl of AA in pore:
D/t repulsion of like charges- K+ ions push each other along as more come into pore
Na+/ K+ channels are gated by:
membrane potential or voltage
What happens in voltage gated channels in response to changes in membrane potential?
Conformational change
Voltage gated sponsors
S1-s4
Pore of voltage gated channels:
S5-s6
The duration of the open state can be controlled by length and flexibility of this part of the channel:
Ball and chain
The ball and chain model inactivation domain is the:
Ball
What creates a binding site for the + charged ball in the mouth of the pore?
Depolarization
What happens when the ball binds to the mouth of the pore:
It is inactivated by occlusion.
How many AA units make up ball:
20; Zaidia talked about 1st 40 AA important for closing the channel
Ex of ligand gated ion channel
Acetylcholine receptor
Present on post-synaptic side
Binds acetylcholine and open channel
Equally permeable to Na+ and K+
Pentamer of 4 kinds of membrane spanning (a2ßdelta) arranged in the form of a ring that creates a pore through the membrane
Ligand gated Acetylcholine receptor
5 subunits come together to form a pore
Ach receptor
The most important manifestation of membrane transport- the basis for communication in the nervous system
Neurotransmission
Nerve impulse is an ______ _______ produced by the flow of current across the plasma membrane of a neuron.
Electrical signal
K+ and Na+ content inside of neuron
High [K+] and low [Na+]
How is the K+/Na+ gradient generated?
Na+/K+ ATPase
This is used to calculate membrane potential
Nernst equation
Action potential rise from large transient
Changes in the permeability of axonal membrane to ions
Conduction for _____ changes first d/t opening of ____channels
Na+; Na+
__________ increases permeability to Na+ which begin to flow in via the Na+ chanel d/t high [ ] outside
Depolarization
After Na+ rush in ________ then opens K+ channels and K+ move out
Depolarization
Sequence of AP
- resting pot. -60mV
- Depolarizing stimulus
- Na+ channels open
- Rapid Na+ entry-further depolarization
- Na+ channels close, K+ open
- K+ move out
- Membrane hyperpolarization
- K+ channels close
- Cells return to resting potential
Synaptic transmission steps:
- AP reaches presynaptic terminal
- Depolarization opens up the VGCC
- Ca++ enters cell
- Causes fusion of synaptic vesicles
- exocytosis- release of NT in synapse
- NT binds to receptor on post-synaptic side
- opens up ligand gated Na+ channel
Special form of ion channel
Called “cell to cell’ channels
Passages btw contiguous cells
Important role in cell to cell communication
Gap junctions
Packed in hexagonal array
Lumen ~20å
Distance btw gap junctions of 2 adjacent cells is ~35å
Structure of gap junctions
Properties of gap junctions:
Small hydrophilic molecules and ions pass through
< 1 kDA molecules can pass: sugars, AA, and nucleotides can pass thru
Proteins, polysaccharides and nuclei acids cant pass
Allow direct communication
Gap junctions
Structure of gap junctions
12 molecules of transmembrane protein= connexin
6 connexin molecules hexagonally arrayed to form a half channel= connexon
2 connexons join end to end in the intercellular space to form functional channel.
Physiological relevance gap junctions in cardiac tissue:
Synchronous response to stimuli - contraction in synchrony
Significance of gap junctions in lens and bone
Distribute nourishment:
Sealed by high Ca+ and H+: protect norm cells from injured or dying cells b/c too much inside of too little outside can be fatal
The induction of biological effects in cells that are not directly traversed by a charged particle
The bystander effect
Differ Ion channels and GAP junctions membrane location:
Gap junctions: transverse 2 membranes
Ion: 1 membrane
Differ Ion channels and GAP junctions connections:
GAP: connect cytoplasm to cytoplasm
Ion: Cytoplasm to ECM
Differ Ion channels and GAP junctions synthesis:
GAP: synthesized by 2 different cells
Ion:
Differ Ion channels and GAP junctions duration of acticity:
GAP: remain open for sec to min
Ion: open for only msec
Water channels
Aquaporins
Increase rate of water flow across membranes
Found in RBC, kidney, cornea
24 kDa protein
Have 6 transmembrane alpha helical domains
Aquaporins
Structure of aquaporins
6 transmembrane alpha helical domains
