Week 5 - Ion Channel Physiology

Question 1

Webpage

Good for a resource

Question 2

Ion channels are where

Answer 2

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

Question 3

Which of the following substances will be least likely to diffuse through a pure phosopholipid bilayer membrane that contains no proteins?

Answer 3

Ions (Na) has most trouble

Water also has a dipole so it is difficult to get across

Question 4

Critical Fact #1

Application of this will be on test

Answer 4

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

Question 5

Ion channels vs Transporters

Answer 5

• 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)

Question 6

What happens when a channel or a trasporter moves ions across a membrane?

Critical fact #3

Answer 6

A current is created**

Use ohms law: V = I R

and if there are not ions being transported there IS NO CURRENT

Question 7

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.

Answer 7

Water molecules enter the RBCs causing them to lyse (swell up and explode)

This is called osmosis

Question 8

Aquaporins

Answer 8

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.

Question 9

What happens when a cell with NO aquaporins is put in a hypotonic solution?

Answer 9

Nothing happens.

Question 10

Critical Fact #2

Answer 10

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

Question 11

Selectivity

Answer 11

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+
  *

Question 12

Gating

Answer 12

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)

Question 13

Inactivationf

Answer 13

Inactivation is another way to close the channel

If wan to close the channel, 2 processes:

• Close Gate
• Inactivate

Question 14

Ion Channel Structure - Draw it

Answer 14

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

Question 15

Which of the following is LEAST likely to pass through an individual channel?

Answer 15

5. Na+ and Cl- (no channel does both anions and cations) Why? becuase of the charge difference.

Question 16

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

Answer 16

4. 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…

Question 17

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).

Answer 17

All gated channels can close; only some channels can inactivate.

Question 18

Summary of Ion Channel Properties

Answer 18

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

Question 19

Gate vs inactivating

Answer 19

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.

Question 20

Membrane poteintial

Answer 20

Mechanims by which the channel is going to have potential to do work

Question 21

True or False:All cells have a resting membrane potential?

What about al LIVING cells?

Answer 21

True. 0 is still a membrane potenetial

True. All live cells have a negative resing membrane potential. All cells in all systems

Question 22

Basic Definitions

Answer 22

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.

Question 23

How many different types of channels are there?

One for each major ion = 4
Hundreds
Thousands
Millions

Answer 23

Hundreds

Question 24

How many of each type of channelare functional in an individual cell?

One
Hundreds
Thousands
Millions

Answer 24

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

Question 25

Critical fact 3

Answer 25

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 (n**eurons and myocytes) have a much **larger RMP** (-30 to -70 mV) because they have a larger number of K+ channels open at rest.

Question 26

Electrochemical Gradient

Answer 26

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

Question 27

Identify the MOST ACCURATE ranking ofEXTRACELLULAR ion concentrations

Answer 27

1. Na \> Cl \> K \> Ca Sodium is most extracellular Potassium is most intracellular Potassium is very very important

Question 28

Identify the ion whose concentration gradient normally favours movement of the ion from INSIDE to OUTSIDE

Answer 28

Only potassium\*\* has a concentration gradient to go from inside cell to outside cell

Question 29

Ion Concentrations in and out of cells

Answer 29

Potasium is very tightly regulated. Potassium stored in intracellular muscle cells\*\*

Question 30

Determinants of Ion Concentrations

Answer 30

Extracellular * Diet * Kidneys (urine) Intracellularly * Transporters * Na / K ATPase (3 Na out, 2 K in) * **Different in every cell\***

Question 31

True or False: Under normal conditions, in living cells,concentration gradients do not “run down”

Answer 31

True - transporters (as long as you have ATP around) will maintain the gradients **Transporters set up the gradients, ion channels use the gradients\*\***

Question 32

Critical Fact #4

Answer 32

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.

Question 33

Resting membrane potentials

Question 34

True or False: Each ion can only move in one direction across the cell membrane (e.g., Na+ in; K+ out).

Answer 34

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

Question 35

Critical fact #5

Answer 35

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\*\***

Question 36

Equilbrium (reversal) Potentials and the Nerst Equation

Answer 36

Erev = 61/2 log []o / []i Concentration out / concentration in (conc grad)

Question 37

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

Answer 37

= 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.

Question 38

Do same quetion for sodium..

Answer 38

Potassium always goes out of cell

Question 39

Critical Fact #6

Answer 39

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.