Download Lecture 4 revised 1/10 How do neurons transmit information over

Lecture 4
revised 1/10
How do neurons transmit information over long distances? In cellular terms, the distances
are very large. Transmitting the information you need to sense, process, and act on the
outside world through a mechanism such as passive diffusion of a second messenger
would slow life to a crawl.
Neurons have evolved mechanisms for using pulses of electrical current, known as action
potentials, to transmit information rapidly over long distances. For example, motor
neurons in your lumbar spinal cord transmits action potentials over a distance of about a
meter to control your toe muscles, and you can very quickly cause these muscles to
contract or relax.
Today we’ll…
1. observe typical responses of a neuron to electrical stimulation
2. note the general properties of an action potential
3. learn how ionic gradients and selective permeability together determine the
resting potential of a neuron
4. note how changing permeability of a membrane to an ion (sodium) can generate
the major excitatory current of the action potential
Fig. 2.1- different types of electrical responses when record from a few locations in NSresting potential, receptor potential, synaptic potential, action potential
Fig. 2.2- experiment- put an electrode in neuron, measure voltage relative to reference
electrode (latter extracellular)
Note neuron is at a negative potential relative to reference.
Now, stimulate neuron with current pulses, either hyperpolarizing (i.e. increasing the
difference between the resting potential and reference) or depolarizing. What happens?
With hyperpolarizing pulses, or small depolarizing pulses get a response similar to what a
resistor and capacitor wired in parallel give (remember RC circuits from physics class?)
If the current pulse causes voltage across neuronal membr to exceed threshold, you get an
action potential- membrane potential rapidly crosses zero to a positive voltage and then
declines back below resting potential.
Normally, depolarization would occur via a receptor potential or summation of synaptic
potentials.
What is it that’s so important about the action potential?
See fig. 3.10, passive current flow.
Now compare to fig. 3.11, and the overhead/handout- recording action potential at a
distance. This is the key, the action potential regenerates, the signal doesn’t dissipate with
distance.
So how is an action potential generated?
First we’ll figure out how resting potential is generated.
A combination of pumps- with specificity for particular ions, and channels- with selective
permeability generates ion concentration differences across membranes
Start w/ simple system, membrane permeable just to K+. Go thru fig. 2.4, concept of
electrochemical equilibrium. If start w/ different conc.s of K+ on both sides of membrane
permeable only to the K+ (not the Cl-), the K+ ions flow such that the electrical and
chemical forces balance, so there is no net current. The resulting state is called
electrochemical equilibrium.
The electrical potential generated across the membrane at electrochemical equilibrium
can be predicted for this sort of 1-ion system using the Nernst equation.
The Nernst equation incorporates the concentration of the ion on both sides of the
membrane, and its charge. Other factors, such as temperature and the gas constant, can be
incorporated into a constant for typical experimental situations.
Note that for an ion with a valence of 1, a 10-fold difference in concentration corresponds
to 58 mV of electrical potential. The sign of the potential depends on the direction of the
concentration gradient and the valence of the ion.
Well, so one ion can give us a resting potential. But how does one get an action potential
through ionic gradients?
The key is first there are multiple different ion gradients
And second the permeability of the membrane changes during an action potential
Note that if the membrane is impermeable to an ion, that ion does not contribute to the
membrane potential.
Fig. 2.6, a simple view of how K+ and Na+ combine to give the action potential voltage
changes.
How can one predict the membrane voltage with multiple different ionic gradients and
permeabilities? The Goldman equation. Note that if P=0, that ion doesnt contribute. Note
that with one ion, collapses into the Nernst equation.
How was it proven that such ionic gradients are responsible for resting potential?
Fig. 2.7, K+ and resting potential; used squid giant axon, favorite prep for a while
because its big (almost a mm in diameter, easier to use the early electrodes) and cheap.
How was it shown that Na+ was responsible for the rising phase? Fig. 2.8
Nomenclature of action potential-Box B figure
rising phase- rising from resting potential
overshoot phase- shoots above 0 mV
falling phase- falls back toward rest
undershoot phase- membrane hyperpolarizes below resting potential
So now we have a general idea of where resting potential and action potentials come
from, next time well explore how action potentials are generated and propagate down an
axon in more detail.
In a multi- ion system, how can you predict membrane voltage? Recall the Goldman
equation; note that it collapses to the Nernst eqn when P (permeability)=0, we discussed
how if an ion is impermeant, it can't contribute to membrane voltage.
Thus, the voltage across the membrane at any given time is determined by the differences
in ion concentration across the membrane, and the relative permeability of the membrane
for the different ions.
So, have we explained the action potential? Yes, and No. We've explained how changing
the permeability to the ions Na+ and K+ can result in the voltage changes. But how/why
does the permeability of the membrane change as a function of time during an action
potential?
The answer is that the permeability of the neuronal membrane is voltage dependent.
How can permeability be measured as a function of voltage and time to study this? The
answer is a tool called the voltage clamp.
Box 3A, Ch. 3.
The idea is to use feedback circuitry to hold the membrane voltage to a particular value,
and see how much current it takes to do this as a function of time.
So, what happens when voltage clamp a squid axon?
Fig. 3.1; here again, hyperpolarization didn't result in any spectacular current flow (just a
capacitative current due to passive membrane properties- charging of membrane to new
voltage), whereas depolarization gives a transient inward current then a delayed outward
current (in/out are w/ respect to inside/outside of cell).
Thus, depolarization caused a voltage-dependent change in membrane conductance!
How many and which ions change permeability w/ depolarization?
Change voltage that clamp to, see how much current flows, fig. 3.2.
This gives a clue as to which ions likely to be responsible for the currents. See how
current amplitude changes with voltage.
Recall Nernst equation. If ion conc's stay the same during a voltage clamp expt (they will
for a while), the amount of current a given ion carries approaches zero as voltage you
clamp membrane to approaches Equilibrium potential for that ion
Current for an ion becomes zero (no net current) at equilibrium potential. If look at
current flow for voltage clamps on either side of equilibrium potential, its direction is
opposite. Thus, in voltage clamp expts, refer to a reversal potential, the voltage at which
the direction of a current reverses. This gives a big clue as to which ion carries that
current if you know the equilibrium potentials for the different ions.