bmed 3100 L2

bmed 3100 L2 - Cell
Physiology
2:
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Unformatted text preview: Cell
Physiology
2:
 Membrane
transport,
 electrophysiology
 August
25,
2011
 Membrane
Transport
 Transport
across
cell
membranes
 •  Solute
concentra?on
differences
 between
ICF
and
ECF
are
extremely
 important
in
life
of
cell
 •  How
are
these
differences
brought
 about?
 •  Transport
of
solutes
either
through
 lipid
bilayer
or
through
proteins,
 occurs
by:
 1.  Diffusion
 2.  Ac?ve
Transport
 Diffusion
 •  Thermal
mo?on:
molecules
 of
any
substance
constantly
 move
 –  Speed
depends
on
 temperature
and
mass
of
 molecule
 –  Direc?on
is
random
 •  Diffusion
 –  Movement
of
molecules
 from
one
loca?on
to
another
 based
solely
on
this
random
 thermal
mo?on
 Diffusion
equilibrium:
Two
one‐way
fluxes
are
equal
in
magnitude
 J
=
PA(CA‐CB)
 Diffusion
Sample
Problem
 •  Two
1‐L
compartments
are
separated
by
a
 urea
permeable
membrane.
Compartment
A
 contains
3
mM
urea.

Compartment
B
contains
 5
mM
urea.


 –  In
what
direc?on
will
the
net
flux
of
urea
take
 place?
 –  When
diffusion
equilibrium
is
reached,
what
will
 the
concentra?on
of
solute
be?
 Simple
Diffusion
 •  Does
not
require
carrier
 protein
 •  Two
pathways:
 –  Through
inters?ces
of
lipid
 bilayer
(lipid‐soluble
 substances)
 –  Through
watery
protein
 channels
(water‐soluble
 substances,
including
ions)
 Simple
Diffusion
through
Protein
 Channels
 •  Protein
channels:
 –  Selec?vely
permeable
 •  Diameter
 •  Shape
 •  Charge
 –  Most
are
open
and
closed
 by
gates
 •  Voltage‐ga?ng
 •  Ligand‐ga?ng
 Facilitated
Diffusion
 (carrier‐mediated
diffusion)
 •  S?ll
downhill,
no
energy
 required.
 At
low
solute
concentra?on,
 facilitated
diffusion
is
faster
 then
simple
diffusion

not
 true
at
high
concentra?ons
 
WHY?
 Primary
Ac?ve
Transport
 Ex:
Na+‐K+
ATPase
 •  Characteris?cs
 –  In
all
cells
 –  Uphill,
requires
ATP
 –  Requires
carrier
proteins
 –  Electrogenic
(more
+
charge
pumped
 out
than
in)
 –  Maintains
concentra?on
gradients
for
 Na+
and
K+
 •  Cycling
between
E1
and
E2
 1.  E1:
binding
sites
face
ICF,
high
affinity
 for
Na+,
bound
ATP
 2.  3
Na+
bind
 3.  ATP

ADP
and
Pi
 4.  E2:
binding
sites
face
ECF,
high
 affinity
for
K+
 5.  3
Na+
released
and
2
K+
bind,
and
Pi
 released
 6.  Binds
ATP
again…
 Secondary
Ac?ve
Transport
 •  Transport
of
2
or
more
solutes
is
coupled
 •  The
downhill
movement
of
one
solute
 provides
energy
for
the
uphill
movement
of
 the
other
solute
 •  Two
types:
 1.  Cotransport
 2.  Countertransport
 Cotransport
 Ex:
Na+‐glucose
cotransport
 •  Na+/K+
ATPase
creates
 storehouse
of
energy
 due
to
excessive
Na+
in
 ECF
 •  Binding
by
BOTH
rotates
 the
cotransport
protein
 and
releases
both
in
the
 cell
 Countertransport
 Ex:
Ca2+‐Na+
countertransport
 •  BOTH
Na+
and
Ca2+
 must
bind
(Na+
on
 ECF
side,
and
Ca2+
pn
 ICF
side)
 •  Is
this
electrogenic?
 Osmosis
 •  Net
movement
of
water
caused
by
a
 concentra?on
difference
of
water
 (mOsm/L)
 g
=
#
par?cles
per
mole
in
solu?on
(Osm/mol)
 C
=
concentra?on
(mmol/L)
 –  Isosmo?c
 –  Hyperosmo?c
 –  Hyposmo?c
 Osmo?c
Pressure
 Pressure
required
to
stop
osmosis
 Atm
or
mmHg
 g
=
#
par?cles
per
mole
in
solu?on
(Osm/mol)
 C
=
concentra?on
(mmol/L)
 σ
=
reflec?on
coefficient
 (1
if
membrane
is
impermeable
to
solute;
0
if
freely
permeable)
 R
=
gas
constant
(0.082
L‐atm/mol‐K)
 T
=
absolute
temperature
(K)
 –  Isotonic
 –  Hypertonic
 –  Hypotonic
 Osmosis
Sample
Problem
 •  The
osmolarity
of
a
solu?on
of
50
mmol/L
 CaCl2
is
closest
to
the
osmolarity
of
which
of
 the
following:
50
mmol/L
NaCl,
100
mmol/L
 urea,
150
mmol/L
NaCl,
or
150
mmol/L
urea?
 –  Urea
does
not
dissociate
in
solu?on
 g
=
#
par?cles
per
mole
in
solu?on
(Osm/mol)
 C
=
concentra?on
(mmol/L)
 Osmosis
Sample
Problem
 •  Assume
that
a
membrane
separa?ng
2
 compartments
is
permeable
to
urea
but
not
 NaCl.
If
compartment
1
contains
200
mmol/L
 of
NaCl
and
100
mmol/L
of
urea,
and
 compartment
2
contains
100
mmol/L
of
NaCl
 and
300
mmol/L
of
urea,
which
compartment
 will
have
increased
in
volume
when
osmo?c
 equilibrium
is
reached?
 g
=
#
par?cles
per
mole
in
solu?on
(Osm/mol)
 C
=
concentra?on
(mmol/L)
 Electrophysiology
 Equilibrium
Poten?als
 •  Membrane
poten?al:
 −  Separa?on
of
charges
that
exists
across
cell
 membranes
 •  Electrochemical
gradient
 −  Direc?on
and
magnitude
of
ion
fluxes
across
 membranes
 −  Depends
on
 1.  Concentra?on
difference
 2.  Electrical
difference
(membrane
poten?al)
 •  Diffusion
poten?al
(mV):
 –  Poten?al
difference
across
a
membrane
 when
an
ion
diffuses
downhill
 –  Generated
only
when
membrane
is
 permeable
to
that
ion
 •  Equilibrium
poten?al:
 –  The
diffusion
poten?al
that
exactly
balances
 tendency
for
diffusion
 Nernst
Equa?on
 •  Used
to
calculate
equilibrium
poten?al
for
an
ion
 at
a
given
concentra?on
difference
across
a
 membrane
 61
 [Ce]
 Eion
=
 z
 log
 [Ci]
 •  z
=
Charge
of
ion
 •  Ci
=
intracellular
concentra?on
(mmol/L)
 •  Ce
=
extracellular
concentra?on
 ‐Always
calculates
poten?al
inside
cell
 ‐Ex: 
‐70mV

poten?al
difference
is
70mV
with
the
inside
of
the
cell
being
 nega?ve.
 Nernst
Equa?on:
 Sample
Problem
 •  If
intracellular
[Na+]
is
15
mEq/L
and
the
 extracellular
[Na+]
is
145
mEq/L,
at
what
 poten?al
difference
across
the
cell
 membrane
will
Na+
be
at
electrochemical
 equilibrium?
 61
 [Ce]
 Eion
=
 z
 log
 [Ci]
 Goldman
Equa?on
 •  The
contribu?on
each
ion
makes
to
the
 membrane
poten?al
 –  Electrical
charge
of
ion
 –  P
of
membrane
to
ion
 –  Ce
and
Ci
 •  Ions
with
highest
conductance
(permeability)
 drive
poten?al
toward
their
own
equilibrium
 poten?als
 Em= 61 log PK[Ke] + PNa[Nae] + PCl[Cli] PK[Ki] + PNa[Nai] + PCl[Cle] Goldman
Sample
Problem 
 •  What
is
the
total
equilibrium
poten?al
of
a
 membrane
permeable
to
K+,
Na+,
and
Cl‐?


 Em= 61 log PK[Ke] + PNa[Nae] + PCl[Cli] PK[Ki] + PNa[Nai] + PCl[Cle] Ion
 ECF
 ICF
 P
 Na+
 145
 15
 0.01
 Cl‐
 100
 7
 0.5
 K+
 5
 150
 1
 How
Do
Muscles
Contract?
 Topics
 1.  Transmission
of
informa?on
throughout
the
nervous
 system
 –  Ac?on
poten?als
 2.  How
informa?on
is
transmiqed
from
the
nervous
 system
to
effector
muscle
 –  Synapses

 •  NMJ
 3.  How
this
transmiqed
informa?on
leads
to
muscle
 contrac?on
 –  Excita?on‐contrac?on
coupling
 Transmission
of
Informa?on
 •  Ac?on
poten?als:
 –  Transient
changes
in
membrane
poten?al
from
rest

electrical
 signals
 –  Neurons
communicate
with
each
other
through
these
signals
 –  Changes
in
membrane
poten?al
due
to
changes
in
permeability
 of
cell
membrane
to
ions
 •  Gated
channels
 –  Very
rapid
 –  Exist
in
excitable
cells
 Res?ng
Membrane
 Poten?al
 •  Poten?al
differences
across
membrane
of
excitable
cells
 between
ac?on
poten?als
(at
rest)
 •  For
large
nerve
fibers:
‐90
mV
 •  Inside
of
cell
always
nega?ve
 •  Holds
steady
 •  Depends
on
 •  Differences
in
specific
ion
concentra?ons
in
ICF
and
 ECF
 •  Differences
in
membrane
permeabili?es
to
the
 different
ions
(#
of
open
channels)
 •  Contribu?on
of
K+
 •  Contribu?on
of
Na+
 •  Contribu?on
of
Na+/K+
pump
 Ion
 ECF
 ICF
 Na+
 142
 14
 K+
 4
 145
 Ac?on
 Poten?als
 ‐ Drama?c
electrical
 impulses
in
excitable
cells
 ‐ Rapid
changes
in
 membrane
poten?als
 •  Res?ng
membrane
poten?al
 •  Depolariza?on
 •  Repolariza?on
 •  Hyperpolariza?on
 Local
Anesthe?cs 
 •  How
might
these
work?
 Propaga?on
of
Ac?on
Poten?als
 •  Spread
of
local
currents
(one
direc?on)
 •  All‐or‐nothing
principle
 Conduc?on
Velocity
 •  Speed
ac?onal
poten?als
are
conducted
along
 nerve/muscle
fiber
 •  Influenced
by
 1.  Nerve
diameter
 •  The
larger
the
diameter,
the
faster
the
 propaga?on
 •  Less
resistance
to
local
currents
 2.  Myelina?on
 •  •  •  Lipid
insulator
of
nerves
 •  More
difficult
for
ions
to
flow
in
and
 out
of
cell
 •  Local
current
can
flow
faster
 Has
lower
concentra?on
of
voltage‐gated
Na +
channels
 Nodes
of
Ranvier:
uninsulated
areas
 •  Why
do
we
need
them?
 •  Saltatory
conduc?on
 •  •  •  APs
jump
from
node
to
node
 Speeds
conduc?on
velocity
 Conserves
energy
 Topics
 1.  Transmission
of
informa?on
throughout
the
nervous
 system
 –  Ac?on
poten?als
 2.  How
informa?on
is
transmiqed
from
the
nervous
 system
to
effector
muscle
 –  Synapses

 •  NMJ
 3.  How
this
transmiqed
informa?on
leads
to
muscle
 contrac?on
 –  Excita?on‐contrac?on
coupling
 ...
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