Week 5 - Ion Channel Physiology Flashcards
Webpage
Good for a resource
Ion channels are where
Every cell in every system
Hundreds of drugs act on ion channels
Excitabe cells, myocytes (muscle cells), neur cells - they are just an extreme example of cells that use ion channels
Which of the following substances will be least likely to diffuse through a pure phosopholipid bilayer membrane that contains no proteins?
Ions (Na) has most trouble
Water also has a dipole so it is difficult to get across
Critical Fact #1
Application of this will be on test
A cell’s phospholipid bilayer limits the passage of charged molecules (especially ions) across the cell membrane (i.e., the lipid part of the cell membrane has high electrical resistance).
Gap junctions (electrical synapses), membrane transporters and ion channels provide routes for charged molecules to cross the cell membrane.
Transporters and channels have fundamentally different properties
Ion channels vs Transporters
- Transporters can be passive or active (req ATP )
- Transporters can go with or against concentration gradient (active goes against)
- Ion channels are passive - molecules are ONLY going to move with the concentration gradient
- Ion channels are a hole in the membrane - direct connection between intracellular and extracellular fluid
- Trasporters - no connection between intra and exta cellular fluid.. Uses a conformational change in a protein
- Ion channels move ions (small molecules)
- Transporters can move ions and larger molecules like glucose
- Channels are faster (millions of ions per second)
- Transporters are slower (hundreds to thousands of molecules per second)
What happens when a channel or a trasporter moves ions across a membrane?
Critical fact #3
A current is created**
Use ohms law: V = I R
and if there are not ions being transported there IS NO CURRENT
What happens when red blood cells are placed in a hypotonic solution?
Water molecules enter the RBCs causing them to lyse.
Water molecules exit the RBCs, causing them to become crenated.
There is no net change inwater movement across the RBC membrane.
Water molecules enter the RBCs causing them to lyse (swell up and explode)
This is called osmosis
Aquaporins
Water channel in membrane allowing water to pass through.
During osmosis, water will cross the membrane in the direction towards the HIGH SOLUTE CONCENTRATION
Water will move from Hypotonic to Hypertonic solution - at equilibrium they are isotonic solutions
Bidirectional** water can go through channel in either direction.
*Rotational space inside the aquaporin has selectiviy for water only - a structural filter. It will only allow water to go through even though ions are smaller than water molecules.
What happens when a cell with NO aquaporins is put in a hypotonic solution?
Nothing happens.
Critical Fact #2
Fundamental ion channel characteristics include selectivity and gating (all have this). Channels differ in the number and types of ions they will pass (selectivity).
Channels can be mechanically, ligand and/or voltage gated. In addition to gating, some channels have additional inactivation mechanisms that can prevent the flow of ions through the channel
Selectivity
Selectivity is what goes thorugh the channel.
Has varying degress of selectivity..
- Cation channels: All K+, Na+, Ca2+ (sensory, cells, neurotransmitter receptors)
- Anion channels: negative charge (mitochondria)
- Extremely selective (specific): Let only one of following: Na+, K+, Cl-, Ca2+
*
Gating
Gating - Is the channel open?
Can change between closed state or open state - this is called the open probability of a channel
Types :
- Leak Channel: always open (neurons)
- Mechanically Opened: deform cell membrane it will deform cell and open the membrane (sensory, skin)
- Ligand Binding Channel: ligand binds and changes the conformation of the channel (neurotransmitter)
- Voltage Gated Chennels : excitable cells, (muscle, never)
Inactivationf
Inactivation is another way to close the channel
If wan to close the channel, 2 processes:
- Close Gate
- Inactivate
Ion Channel Structure - Draw it
Have a spot that narrows down, this is called the selectivity filter
Then also have the gate which can open or close
Also has a plug (something that binds to it to plug - not all channels have this)
Hole, Gate, and plug
Which of the following is LEAST likely to pass through an individual channel?
- Na+ and Cl- (no channel does both anions and cations) Why? becuase of the charge difference.
Which of the following is LEAST LIKELYto be directly responsible for opening an ion channel?
Membrane stretch
Random changes in the position of the channel gate
Depolarization of the cell membrane
Change in extracellular ion concentration
Binding of a drug to the channel
- Change in extracellular ion concentration - the channel doesn’t care what the concentration of ions is.
Random changes in position.. proteins can randomly change conformation…
What is the difference betweenclosing and inactivating a channel?
The structure of the selectivity filter is altered during inactivation but not when channels close.
All gated channels can close; only some channels can inactivate.
Ions can flow through inactivated channels, but not through closed channels.
Inactivation is random (true, the plug), but specific mechanisms are used to close a channel (mechanical stimulation, change in membrane voltage, binding of a ligand).
All gated channels can close; only some channels can inactivate.
Summary of Ion Channel Properties
Ion channels are selective to varying degrees
Ions wont cross membrane via diffusion, need a channels or transporters
Channels are leak, mechanically gated, ligand gated, voltage gated
Major parts: selectivity filter, gate, and inactivation plug (maybe)
Can be bidirectional but alwys down concentration gradient
Gate vs inactivating
Gate - somethign does something to open gate, then once that thing is not bound the gate closes eventually
Inactivation is done by a random ligand that plugs the hole.
Membrane poteintial
Mechanims by which the channel is going to have potential to do work
True or False:All cells have a resting membrane potential?
What about al LIVING cells?
True. 0 is still a membrane potenetial
True. All live cells have a negative resing membrane potential. All cells in all systems
Basic Definitions
Membrane potential - difference in voltage between inside and outside (Vm)
If you move it more positive, it is called depolorization
If it moves more negative it is called hyperpolarization
Repolarization returns it to the resting state (regardless of neg or pos change)
No magnitude associated with it.
How many different types of channels are there?
One for each major ion = 4
Hundreds
Thousands
Millions
Hundreds
How many of each type of channelare functional in an individual cell?
One
Hundreds
Thousands
Millions
Thousands - in the membrane on a individual cell
Many types of channels & many of each type in the cell membrane**
Membrane potential of cell is never constant, it is always in a state of flux, the net membrane potential however might be constant
Critical fact 3
All cells have a specific complement of channels, transporters and receptors that, in part, defines their unique physiology. By definition, all cells have a membrane potential.** **
Ohm’s Law defines the relationship among membrane potential (voltage or Vm), current and conductance (the inverse of resistance): I=CV, C is conductance. V = IR
Live cells have a resting membrane potential (RMP) that is negative with respect to the extracellular fluid.
Electrically excitable cells (neurons and myocytes) have a much larger RMP (-30 to -70 mV) because they have a larger number of K+ channels open at rest.
Electrochemical Gradient
Determines what goes in or out of a cell.
Positive ion is going to want to move towards a negative charge, and a negative ions is going to want to move towards a positive charge
Identify the MOST ACCURATE ranking ofEXTRACELLULAR ion concentrations
- Na > Cl > K > Ca
Sodium is most extracellular
Potassium is most intracellular
Potassium is very very important
Identify the ion whose concentration gradient normally favours movement of the ion from INSIDE to OUTSIDE
Only potassium** has a concentration gradient to go from inside cell to outside cell
Ion Concentrations in and out of cells
Potasium is very tightly regulated.
Potassium stored in intracellular muscle cells**
Determinants of Ion Concentrations
Extracellular
- Diet
- Kidneys (urine)
Intracellularly
- Transporters
- Na / K ATPase (3 Na out, 2 K in)
- Different in every cell*
True or False: Under normal conditions, in living cells,concentration gradients do not “run down”
True - transporters (as long as you have ATP around) will maintain the gradients
Transporters set up the gradients, ion channels use the gradients**
Critical Fact #4
The primary function of neuronal Na+/K+ ATPase is the establishment of the concentration gradients for Na+ and K+ that are needed to generate resting, graded and action potentials.
The actions of Na+/K+ ATPase are only mildly electrogenic: the net result of the actions of Na+/K+ ATPase is a Vm of ~-5 to -12 mV.
-These transporters DO NOT maintain the membrane potential… Yes you will get a membrane potential but ion channels are MAINLY responsible for maintaining the membrane potential.
Resting membrane potentials
True or False: Each ion can only move in one direction across the cell membrane (e.g., Na+ in; K+ out).
False. They can move both ways.
- Ions move through channels in both directions
- Concentrations gradients dont change
- Can have an electrical gradient and a chemical gradient - these determine potential and magnitude
Critical fact #5
For each ion, the equilibrium (or reversal) potential is the membrane potential where the net flow through any open channels is 0.
In other words, at Erev, the chemical and electrical forces are in balance. Erev can be calculated using the Nernst equation. In mammalian neurons, the equilibrium potential for Na+ is ~+60 mV and for K+ is ~-88 mV.
Must be able to calculate this and understand it**
Equilbrium (reversal) Potentials and the Nerst Equation
Erev = 61/2 log []o / []i
Concentration out / concentration in (conc grad)
If [Ca2+]o = 1 mM and [Ca2+]i = 10-7 mM,what is the reversal potential for Ca2+?
-214 mV
-61 mV
0 mV
+61 mV
+214 mV
= 61/2 * log 1/10^-7 = +214 mV
Very high reversal potential so it will go into cell. There is really no other way for it to go. It will always go into cell.
Do same quetion for sodium..
Potassium always goes out of cell
Critical Fact #6
In order to determine the RMP, we must account for the **RELATIVE **contribution of each channel type, which is expressed in terms of permeability (P). The resting membrane potential will be close in value to the reversal potential for the ion that carries the majority of the resting current.
