Professional Documents
Culture Documents
Physiology - Lecture 2 PDF
Physiology - Lecture 2 PDF
physical
Receptor
chemical
stimulus response
acquiring
excitability
coordinating
Selective
membrane
identity permeability disseminating
evolution
adaptability
Selective membrane permeability:
The lipid barrier of the cell membrane and cell membrane transport proteins
Chemical compositions of
extracellular and intracellular fluids.
“Diffusion” Versus “Active Transport”
1.Diffusion
-Simple diffusion:
- lipid-soluble subst. (O2, CO2, alcohols) through intermolecular
spaces of the lipid barrier
- through a membrane opening - protein channels (e.g., water,
lipid-insoluble molecules that are water-soluble and small
enough):
selective permeable channels
non-gated OR gated (open/closed by gates)
voltage-gated
ligand-gated (chemical-gated)
-Facilitated diffusion = carrier mediated diffusion
e.g. transport of most of aminoacids and glucose
2.Active transport
- Primary active (pumps)
- Secondary active (co- and counter-transport)
Simple diffusion through protein channels
VOLTAGE GATED:
-for Na+ channel:
strong negative charge on the inside of the cell
membrane outside Na+ gates remain tightly closed
when the inside of the membrane loses its negative charge, these gates would
open suddenly and allow tremendous quantities of Na+ to pass inward through the
sodium pores.
-for K+ channel:
gates are on the intracellular ends of the K+ channels, and they open when the
inside of the cell membrane becomes positively charged.
The concentration of (-) ions is initially the same on both sides of the membrane, but a (+) charge
applied to the right side of the membrane and a (-) charge to the left, creates an electrical gradient
across the membrane, moving the ions... When the concentration difference rises high enough, the
two effects balance each other.
EMF = +/-61 log C inside/C outside at 37°C for any univalent ion (z=1), as Na+ or K+
R = gas constant, F = Faraday constant, z = valence, T = temp; C = ion conc.
(+) for negative ions / (-) for positive ions, diffusing from inside to outside.
Diffusion and the cell membrane potential
Internal membrane potential is negative when K+ diffuse and positive when Na+
diffuse because of opposite concentration gradients of these two ions.
Calculation of the diffusion potential when the membrane is
permeable to several different ions – Goldman equation
(Actual potential)
Calculation of the diffusion potential when the membrane
is permeable to several different ions – Goldman equation
2 - Ion pumps
H+
K+
3Na+
Ca2+
CARRIERS PUMPS
K+
Cl- CHANNELS
K+
Cl-
Ca2+ AA
Na+
Cl-
1. Ion channels
3 1
2
Voltage-gated K+ channel
- components:
- ion selectivity filter for Na+:
Na+ discard the water molecules associated with them in order to pass in single
file through the narrowest portion of the channel
- activation gate that can open and close, as controlled by voltage sensors,
which respond to the level of the membrane potential
- inactivation gate limits the period of time the channel remains open, despite
steady stimulation.
PCP- phenylciclidine
Gated (active) Ion Channels
Cell
membrane
intracellular
Fibrillary gate
protein
Non-gated (passive) Ion Channels
K+ leak channels
2. Ion Pumps
Functional particularities:
Na+-K+ ATPase pump can run in reverse: If the electrochemical gradients for
Na+ and K+ are experimentally increased enough so that the energy stored in their
gradients is greater than the chemical energy of ATP hydrolysis, these ions will move
down their concentration gradients and the Na+-K+ pump will synthesize ATP from
ADP and phosphate.
The phosphorylated form of the Na+-K+pump can either donate its phosphate to ADP
to produce ATP or use the energy to change its conformation and pump Na+ out of
the cell and K+ into the cell. The relative concentrations of ATP, ADP, and phosphate,
as well as the electrochemical gradients for Na+ and K+, determine the direction of the
enzyme reaction.
For nerve cells, 60 to 70 % of the cells’ energy requirement may be devoted to
pumping Na+ out of the cell and K+ into the cell.
The Na+-K+ Pump
Ca2+
Ca2+
3. Ion Exchangers/
Carriers/Cotransporters
- Na/Ca
- Na/H
- Na/HCO3
- Na/ aa, Na/G
- Cl/HCO3 -
- Na/K/2Cl
- K/Cl, etc
Ion gradients, channels, and transporters in a typical cell (Boron, 2009)
Cell membrane potential –
Resting Membrane Potential
The basis for the resting membrane potential:
Na+-K+ pump K+-Na+ “leak” channels
Humans
[Na+] [K+]
Out 142 4 Membranes are 100X more
permeable to K+, as there
In 14 140
are more leakage channels
Ratios for K+ (see no. of genes…)
Na+ In:Out = 0.1
K+ In:Out = 35.0
A Motor Neuron
Membrane responses to stimulus current
Animation at http://www.sumanasinc.com/webcontent/animations/neurobiology.html
-A stimulus initiates a membrane
electrical change that depend on the
passive properties of the neuronal
membrane
Na+ permeability
increases 500-5000 x
The nerve action potential
Threshold
-Occurs when Na+ entering exceeds K+
leaving
-A rise in potential of 15-30 mV is required
•Membrane is polarized
Resting Stage
i.e., a –90 mV membrane resting potential present
action potential
Ion conductance
Na+ conductance increases faster
and lasts for a shorter duration.
K+ conductance is delayed,
increases slowly and lasts longer
The Action Potential and the
positive feedback of the
Na+ channels activation START
+ feed-back
Roles of other ions than Na+ and K+ during the AP
•Impermeant anions inside the nerve axon…
•Calcium Ions:
- calcium pump pumps calcium ions from the interior to the exterior of the cell
membrane (or into the endoplasmic reticulum of the cell), creating a calcium ion gradient
of about 10,000-fold (internal cell conc ~10-7 molar).
- voltage-gated calcium channels slightly permeable to sodium ions as well as to
calcium ions; when they open, both calcium and sodium ions flow to the interior of the
fiber = Ca++-Na+ channels. The calcium channels are slow to become activated (slow
channels), requiring 10 -20 x as long for activation as the sodium channels
(Shrager Lab)
Na channels distribution and
generation of AP in axon hillock
- initial depolarization at the axon hillock +f.b. for Na+ channels critical
membrane potential = threshold (all-or-none response)
-AP: depolarization and repolarization, followed by afterhyperpolarization, as
K+ channels remain open and membrane permeability for K+ is higher
- propagation of AP to the axon terminals synapses
- also backpropagation in the soma & dendrites, without regenerating in the somal
membrane, as somal membrane has too few Na+ channels to regenerate APs; also,
inactivation of Na channels at axom hillock (here, refractory period).