Transcript Ion Channels

A phospholipid segment Hydrophilic head,
hydrophobic tail Watson, The Cell
Classes of proteins bound within the lipid
bilayer, Watson, the Cell
The DNA double helix contains the
information for protein manufacture
• The four base pairs are made up of :
•
Adenine, (A)
•
Cytosine, (C)
•
Guanine, (G)
Thymine, (T)
The base units are always paired in the DNA
double helix
• Adenine always pairs with thymine:
•
A -T or T- A
• Cytosine always pair with guanine:
•
C - G or G - C
Directional specificity to the DNA stepladder
• Both DNA and RNA have a directional
specificity.
• At one end of the chain the free phosphate
group is attached to the 5’ atom of the first
sugar, at the other end to the 3’ atom of
the last sugar has no phosphate group.
• The two strands are antiparallel, they run
in opposite directions.
The Double helix
• The base pairs make the steps of a model
organic ladder of the double helix holding
the two twist together, while the ribose
sugar makes up the outside hand-rails of
our model organic ladder.
The double helix step-ladder
Central Dogma of molecular biology
Aidley & Stanfield, Ion Channels
The role of mRNA
• RNA acts as an intermediary between
DNA and the protein.
• RNA codes the complementary base pair
of one DNA strand with uracil (U) pairing
with adenine in place of thymine.
• A, C and G pairing with T, G and C.
The central dogma the idea of a genetic
code
• A set of rules that relates groups of bases
on mRNA to amino acids which determine
the protein.
• The Rule: three sequential bases (forming
a codon) code for each amino acid.
• There are 64 possible combinations, 43
. Three triplets are known as stop codons.
mRNA is read sequentially from the 5’ end.
• Each successive amino acid is added to
the developing protein chain.
• The α-amino group combines with the αcarboxyl group of the previous member to
form the peptide linking of the two.
• The first member of the chain has a free
amino acid, the N terminus, and the last
has a free carboxyl group, the C terminus.
Not all section of the mRNA are the
same.
• There are transcription control regions as
well as the part that forms the primary
RNA molecule.
• The sequence making up a gene contains
a number of sections called exons, which
encode parts of the protein sequence
separated by introns (intervening
sequences) which do not.
• http://www.youtube.com/watch?v=n9eWh
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• http://www.youtube.com/watch?v=Yl754_T
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• http://www.youtube.com/watch?v=D5vH4
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Voltage gated channel
Potassium voltage gated channel
• The model assume that channels are
water filled pores through which ions can
pass.
• Effective size of K+ channel is dependent
on the hydrated size of the ion.
• Hydrated K+ is smaller than hydrated Na+
• While K+ is a larger ion than Na+, its ability
to hold on to its water cloud is less than
that of Na+ making Na+ a bigger ion an
unable to pass through a K+ channel.
Channel selective filter for Na+
• Hillel’s thesis: Na+ ions bind transiently at
an active site as it moves through the
channel.
Hillel’s model of a Na+ voltage gated
channel
Amino acid residues in the wall are active
sites for stabilization of the positive charges
ion
• At the binding site the positive charge of
the ion is stabilized by a hydrophilic
negatively charged amino acid residue
lining the channel wall and by a water
molecule that is attracted to a second
amino acid residue lining the other side of
the channel.
• K+ cannot move through a Na+ channel
even though it is a smaller ion because it
can not be stabilized by the negative
charge of the filter.
Chemical vs electrical synapse
Electrical synapse vis-a-vi Chemical
synapse
The Gap junction
Passive channels
• There are passive channels that are
selective to only one species of ion.
• The ion of interest is K+.
• These channels are not effected by
changing voltages across the membrane.
• They are always open and are the basis
for the resting membrane potential
Active channels
• Active channels allow ion to flow through
the channel dependent upon the state of
some physical attribute of the channel,
• Physical attribute:
– Voltage
– Ligand
– Stretch
– 2nd messenger
Active channel can be open, open but
deactivated, blocked or closed
K+ voltages-gated channel
4different types of stimuli that opens gated
channels
Note here the refractory (deactivated) state
Exogenous ligands (drugs) can bias an ion
channel to either open or close
When ion channels open, ions move down
there concentration gradient
• When ions move down their concentration
gradients, electrical current flows in the
direction of the ion movement.
• The magnitude of the current and the rate
of movement of the current follows a
know law (to be discussed next week).