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ION CHANNELS & MEMBRANE POTENTIALS |
| Membrane
Transport :
How Things Get Across a Membrane 4 Ways: 1.
by
DISSOLVING in a membrane
fig |
Skip this material move to Ion Channels
1. by DISSOLVING in a membrane
hydrophobic solutes into a lipid bilayer
Partition vs.
Permeability Coefficients [ see fig ]
2. by membranes ENGULFING particles
movement of large volumes of solute via membrane vesicles
Bulk Transport
Exocytosis [ 14.25 & 14.26 ]
solute packaged membrane vesicles [endomembrane system] fuse
w plasma membrane releases bulk material to outside
Endocytosis
uptake via invagination of exterior cell membrane packaging solutes
into interior membrane bound endocytotic vesicles
- phagocytosis - solid particle uptake by specialized cells… [ 14.27 ]
phagocytes [ macrophages & WBC 14.28
] = phagosomes (>250 nm)
- pinocytosis - liquid uptake into small vesicles (<150nm)
- receptor mediated endocytosis
LDL receptors (cholesterol) (14.29 &
14.18)
Membrane Transport : How Things Get Across a Membrane
3. by CARRIER PROTEINS [ 12.2 ]
protein receptors w specificity for a solute
transport solute through a lipid bilayer
[ bacteriorhodopsin
- light mediated H+ transport 12.4
]
CARRIER MEDIATED TRANSPORT
Facilitated Diffusion
[ 12.6 ]
Active
Transport (Na-Pumps & Proton Pumps) [ 12.8 ]
4. by CHANNEL PROTEINS via diffusion [ 12.2 ]
ions & small hydrophilics move thru a hydrophobic PORE
Action Potentials
[ 12.30 ]
Synaptic Transmissions [ 12.36
]
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Brief Review of Cell Membrane Transport
Unit Membrane Hypothesis:
"all membranes look alike in TEM"
Current structural model - Fluid Mosaic model [ fig 11.4 ]
lipids = phospholipid bilayers [ types of p-lipids fig 11.17 ]
proteins =
[ fig 11.22 ]
a) Integral (intrinsic proteins)...
denatured upon release
b) Peripheral (extrinsic)...
easily extractable
Extra-cellular Matrix-
glyco-proteins secreted by cell, i.e., "a cell wall"
ION [ligand]… atom or group of atoms carrying an electric charge;
ions may exist in solid, liquid, or gaseous environments
have flux rates proportional to lipid solubility (except water)
CARRIER PROTEINS - intrinsic proteins
transport solutes via small, conformational changes in protein shape -
move water soluble molecules
TYPES or KINDS of SOLUTE TRANSPORT – [ 12.12
]
DIRECTIONAL
UNIPORT - one way
SYMPORT - two same way
ELECTROGENIC - one way, charged
ANTIPORT - two way, opposite directions
ELECTROCHEMICAL GRADIENT - driving force is established by
a difference in (conc) or potential... on either side
[ 12.7 ]
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PASSIVE Transport - solute movement w existing
electrochemical gradient
no energy is expended; movement toward equilibrium
[ 12.5 ]
Diffusion - net random thermal motion of a solute
[ hi --> lo ]
Osmosis
- net movement of water from [high] --> [low] [ 12.15 ]
water movement...an anomaly; not lipid soluble, yet
highly permeable
ACTIVE Transport - solute movement against an existing electrochemical
gradient requires energy; movement away from equilibrium
[ 12.8 ]
NaK-ATPase (Na Pump) - carrier actively Na out / K in [ 12.9 &
12.11 ]
COUPLED Transport - transfer of one solute depends upon
simultaneous transfer of 2nd solute
[ 12.8 ]
Na/Glucose cotransport [ 12.14 & 12.14 enhanced ]
CARRIER MEDIATED Transport - Plants vs. Animals systems [ 12.17 ]
Animals - NaK-Atpase = Na gradient
Plants - H+ATPase = H+ gradient
Na driven symport
H+ driven symport
H+ATPase (lysosomes)
H+ATPase (vacuole)
Let's look at role channel proteins
4.
by CHANNEL PROTEINS via
passive diffusion [ 12.2 ]
ions & small hydrophilics
can move thru a membrane hydrophilic PORE
ion channels are
responsible for... Action Potentials
[ 12.30 ]
...
Synaptic Transmissions [ 12.36
]
ION CHANNELS and
Transport
an ion channel is a trans-membrane aqueous pore
formed by a…
CHANNEL PROTEIN - membrane transport proteins which
forms a hydrophilic pore
allowing small molecules and
ions
to move
ions via passive uniport [in/out].
[ 12.2
& 11.25 ]
esp: Na /
K
/ Cl /
Ca
ROLE of Ion Channels -
makes membranes transiently permeable to charged ions
opening of a channel allows rush
(pulse) of electrical charge
in/out
PROPERTIES of Ion Channels ("ionophores" = ion mover)
SELECTIVE - permits only some ions to pass,
and exclude others
PORE SIZE - based upon distance between & distribution
of polar charged aa's (glu, asp, his, lys, arg)
on channel protein [fig]
often
the sphere of hydration of the ions is shed to facilitate transport
-
positive channels: allow - ions to flow & vice versa
Gramacidin model:
cationic bacterial antibiotic ionophore
[ Na+ ]
figure
GATED -
channels exist in OPEN/CLOSED conformation states [ 12.22 ]
VOLTAGE Gated - open state controlled via
cell potential
LIGAND Gated
- controlled by binding of
solute [
as acetylcholine ]
STRESS ACTIVATED- as
with a mechanical force [
auditory hair cells ]
Observing Ion Channels in Action
PATCH CLAMP Recording... Procedures & Equipment & [ 12.20 ]
microelectrode [μm meter glass tube] contacts membrane surface
Taste - an example of how ion channels work. article (Taste Fundamentals)
salty & sour taste are due to ion channels
an Atomic Structural Model of a K+ ion Channel
MEMBRANE POTENTIAL... [Cell's
RESTING POTENTIAL]
- net
distribution of ions across cell is
often not equal
i.e., a non-zero (neutral) distribution results in a charge differential
- leads to voltage differences [+/-] across membranes
- the electric charge exhibited by most typical cells is [ - ]
negative
POTENTIAL - (in electrical terms) is amount of electrical charge
at one point in an electric circuit compared to
some other point in the same circuit
- measured inside vs. outside of cells - via microelectrode
SGA
- 65 mVi
Frog muscle fibers - 90 mVi
Nitella
- 150 mVi
Valonia
+ 15 mVi
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NERNST POTENTIAL [equation - defines passive ion equilibrium] (12.27)
E (mv)
= R T ln [Co]
= +/- 62 lg10 [Co]
zF
[Ci] [Ci]
E(mv) = (1.98) (273 + 37) /
(+/-1) (23,000) [2.303] = 0.062 lg10 [Co]
[Ci]
Causes of Resting Potential - all which make inside
of cell (
- ) NernstEquation
unequal distribution of the "sexy"
ions (Na, K, Ca, Cl, H)
active transport NaK-ATPase
= 3 Na(+) out & 2 K(+) in
differential permeability of
Na (slower in)
& K (faster out)
lots of protein [anions -] inside cells
diffusion of
Cl- in faster than Na in
measured
potential
ACTION POTENTIAL - a self-propagating change in the voltage
i.e., a depolarization or reversal of
resting potential charge across membranes
name given to
changes in electrical charges that occur during
the stimulation of a nerve cell, usually visualized graphically
from an oscilloscope recording
PROPERTIES of an AP
requires a living cell, i.e., requires
O2 for cell metabolism
eliminated by metabolic
poisons as cyanide
measured using
microelectrodes impaled into cells
[fig]
has a threshold - amount of stimulus needed to "fire" an AP
an "all-or-none-phenomena"
rapid – has a time course = 2 to 3
msec
EVENTS DURING an AP
visualization of AP
depolarization - goes from negative to positive
voltage gated Na channel opens
-
Na floods in [ 12.31
& 12.32 ]
potential goes from -70mV to +35mV
(interior goes transiently + )
repolarization - Na channels close &
voltage gated K channels open - K floods out
[
ion channel
changes ]
refractory period - time before another AP can 'fire' [ summary figure ]
CONDUCTION of an AP along an
axon [ 12.33 ]
local spreading of electric charge = change in Na channels
of adjacent membrane regions
autocatalytic - "domino effect"
[ 12.33b ]
Post Synaptic Potential
Synapse - functional connection between neurons
[ 12.34 ]
Synaptic cleft - space between neurons across
Synaptic knob - site of
synaptic vesicles that hold
neurotransmitter (acetylcholine)
Events
-
pre-synaptic side -
AP reaches synaptic knob
opens
voltage gated Ca+2 channel
(Ca floods in) [ 12.35
]
synaptic vesicles fuse w presynaptic membrane
release neurotransmitter into cleft
post-synaptic side - neurotransmitter binds to receptor [ 12.36 ]
postSM receptors are
ligand gated ion channels
ion channels open - change potential charge of
post-synaptic membrane fires a new
AP
removal of stimulus = enzyme (esterase)
destroys transmitter
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Synaptic Events & Neurotransmitters
Excitatory neurons --> open
Na/Ca channels PostSM --> +
-->
AP
neurotransmitters include
acetylcholine &
glutamate...
Chinese
Restaurant Syndrome
Inhibitory neurons
--> open Cl channels --> - -->
no AP
neurotransmitters are GABA and glycine
fig 12.37
Integration of stimuli.... fig 12.38
Effects of Drugs - 1) barbituates & tranquilizers (valium)
bind to GABA-gated Cl channels thus are inhibitory
2) antidepressants (prozac) - blocks reuptake of serotonin (neurotransmitter)
3) psycho active drugs (LSD/mescaline) -
bind to serotonin-dopamine brain cell receptors
Neurotransmitters (tbl 12.3 p 402)
neuro-muscular junction - acetylcholine (contractions)
biogenic amines (CNS) - epinephrine & norepinepherine -
increase heart rate
serotonin & dopamine - affect mood, attention & learning
amino acids -
ASP & GLU -
excitatory (CNS); GLY & GABA - inhibitory
peptides - (small proteins) - endorphins - decrease perception of pain
substance P - excitatory transmitter - signaling pain
Stimulants - chemicals that increase activity of CNS
cocaine - prevents re-uptake of dopamine by synaptic vesicles pre-SM
caffeine - can increases post-synaptic threshold (Cl in... more - ...greater threshold )
also stimulates HR & breathing rate (caffeine
food contents)
barbiturates & valium – intensifies
GABA (inhibitory) effects
Poisons like
strychnine - prevent loss of transmitter ---> muscle tetanus
Neuro-diseases
& Transmitters
Parkinson's is due to a lack of dopamine
schizophrenia is due to too much dopamine
depression is due to a reduced epinephrine-norepinephrine
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