I.
II.
6. The resting membrane voltage is -65 mV, closer to EqK, because the
membrane is much more permeable to potassium than sodium (-10 mV if
they were equally permeable)
a. Means that neither ion is at equilibrium, and thus, both have a net
flux out or into the cell, respectively
b. This flow of ions would eventually lead to the dissipation of the
unequal ionic distribution across the membrane
c. The sodium-potassium pump prevents this loss of ability to create
a resting membrane potential
i. Net outward flux of positive charge electrogenic pump
ii. Alters the balance of Na+ influx and K+ efflux; more
electrical driving force for Na+ to enter, and less electrical
driving force to move K+ out (closer to EqK, further from
EqNa)
iii. Net passive flux through leak channels = active pumping of
ions
Lecture 2: Driving Force and Ion Channels
a. Driving Force
i. The driving force is the push on an ion
ii. DF = Vm - Eqion
1. Negative = inward push of ions
2. Positive = outward push of ions
iii. Conductance, in biological terms, is equal to the flux of ions across the
membrane through protein pores or ion channels
1. Ability of charge to move from one point to another
2. Unit: Siemens (S)
3. Size of conductance depends on the number of charged particles moving
and how fast they move
iv. Resistance refers to how well a cell prevents the flux of ions (i.e. its leakiness)
1. The inverse of conductance (R = 1/g)
2. Unit: Ohms
3. The relative inability of electrical charge to migrate
4. The smaller the cell, the higher the resistance
v. Ohms Law: V = IR
vi.
b. Ion Channels
i. Ion channels are biological units that explain electrical resistance and
conductance. Protein pores that are selective for individual ions are called ion
channels.
ii. Ion channels are often gated by external influence:
1. Voltage potential difference across membrane (VG Na channels)
III.
IV.
i. A variant of the voltage clamp that is easier to perform on smaller cells and allows
the direct observation of ionic current flux through a SINGLE ion channel
ii. Glass pipette with a tiny opening is used to make contact with a patch of the
neuronal membrane; suction applied to seal pipette and membrane
iii. Currents flowing through single channels are called microscopic currents; these
current measurements look like steps; macroscopic currents represent the sum
of the microscopic currents, and the likelihood a channel will be open at a
given time during depolarization of the membrane
b.
c.
d.
e.
V.
about 2000 receptors opened for each mEPP (approx. 5000 ACh
molecules per mEPP)
b. Quantal Nature of Synaptic Transmission
i. Do lots of mEPPs make up one EPP?
1. Katz varied the extracellular ion concentrations, and realized that action
potential-evoked transmitter release required extracellular Ca++
2. When EC Ca++ was dropped to very low levels, the EPP size got smaller
some even nearly as small as mEPPs
3. The above approach was used to accurately measure the size of EPPs and
mEPPs
a. When an EPP occurred, the amplitude was a multiple of the mEPP
amplitude (i.e. EPPs fluctuate in amplitude by the size of mEPP)
b. As the calcium concentration outside was increased, the mEPP size
did not change (at one particular voltage), but the EPP size did
increase
i. Note that the EPP represents a non-linear summation of
quanta as the membrane potential increases, the
smaller the amount is that each quanta contributes to
change in an EPP!! This is due to the change in
membrane potential resulting in a change of driving force!
c. Calcium increases the likelihood that transmitter will be released
ii. The Quantal Theory of Synaptic Transmission
1. Transmitter is only released as a fixed number of molecules (quanta)
a. Occurs via a membrane bound synaptic vesicle that contains
thousands of molecules of transmitter
i. NMJ: 150 quanta per AP within 1 msec
ii. CNS: 1-10 quanta per AP
b. ACh binds to receptor channels, which have equal conductance for
Na+ (in) and K+ (out), and thus, have an Eq = -10 mV
i. The closer Vm is to -10 mV, the less driving force there on
ions to pass through these channels; this results in smaller
mEPPs at higher membrane potentials
2. Occasionally, quanta are liberated spontaneously (e.g. mEPPs)
3. A presynaptic action potential increases the probability that these
quanta will be released (by causing Ca++ to enter the nerve terminal)
iii. Quantal Analysis
1. Assuming that a single vesicle is equal to a mEPP, and that an AP induces
synchronous fusion of many vesicles to result in an EPP, we can try to
understand how strong synapses are, and how strength changes with
synaptic events
2. Quantal analysis determines if a change in strength of communication
between neurons is due to a change on the presynaptic or postsynaptic side
of the synapse
3. If you can measure the size of mEPPs and EPPs, you can divide the mean
EPP/mean mEPP and get the quantal content, m, i.e. the number of
effective quanta/vesicles released in response to a nerve impulse
4. The mean postsynaptic response amplitude can be determined by m =
npq, where:
a. n = number of release sites