Neurophysiology
I. Background
>A. The two main branches of the nervous system:
>>Central Nervous System (CNS)- brain and spinal cord
>>Peripheral Nervous System (PNS)- the rest. Originates from major
nerves (bundles of neurons) coming out of the brain (cranial nerves) and
spinal cord (spinal nerves)
>B. The PNS branches
>>1. Afferent vs. Efferent Divisions
>>>Afferent- "sensory." Brings information to the CNS about sensation
(olfaction, audition, etc), "state of the body" (position of joints & muscles,
stretch of organs, etc), pressure, pain, etc.
>>>Efferent- Brings messages out of the CNS to muscles and glands
(called "effectors")
>>2. The Efferent Division
>>>a. Somatic vs. Autonomic Systems
>>>>Somatic (SNS)- messages sent to skeletal muscle (that's what we
talked about in muscle physiology)
>>>>Autonomic (ANS)- messages sent to cardiac & smooth muscle, and
glands
>>>b. The Autonomic Nervous System
>>>>>Parasympathetic- resting, digesting
>>>>>Sympathetic- exercising, fasting

The para- and sympathetic systems have opposing effects to one
another (ex. para- decreases heart rate, sympathetic increases
heart rate). The quick & dirty introduction to them makes it sound
like either one or the other is functioning, depending on whether
there's an emergency or not. Really, both are typically influencing
different parts of the body to varying extents at any given time.
C. Neuron structure and communication: please review, dendrites, cell
body, axon hillock, axon, axon terminal, telodendria, collaterals,
synapse, synaptic cleft, myelin sheath.
II. Neurophysiology
>A. Background: types of membrane channels and where they cluster on
neurons
>>>1. Chemically regulated: open/close in response to the binding of a
chemical, specifically a neurotransmitter. Most of these are located on
the dendrites and cell body of a neuron.
>>>2. Voltage regulated: open/close in response to a specific change in
voltage. Most of these are located on the axon hillock, along the axon,
and at the axon terminal.
>>>3. Mechanically regulated: open/close in response to some sort of
mechanical stimulus, like pressure or vibration. We probably won’t look
specifically at these; but, for example, they would be located at the
dendrites of sensory receptors that are sensitive to touch/vibration.
>B. The nerve cell at rest
>>1. Leak channels: the membrane of a neuron contains leak channels
for both Na+ and K+. However, it contains MANY more K+ leak channels.
Since more K+ is in the cell than out, K+ passively diffuses down its
concentration gradient through these leak channels to the exterior of the
cell (the opposite is true for Na+). Since there are more K+ channels,
more K+ ions leave the cell than Na+ ions enter. Therefore, more positive
charges leave the cell than enter. This is partially responsible for creating
the slight negative interior of the cell compared with the exterior.
>>2. Sodium-Postassium Exchange pumps- constantly work to pump
Na+ out and K+ in, against their concentration gradients. It's not an even
trade though. 3 Na+ are pumped out for every 2 K+ pumped in. Again,
more positive charge goes out than comes in, helping to create the
relative negative interior of the cell.
>>3. The resting potential of the average nerve cell is -70mV.
*Keep in mind that the electrochemical gradient of sodium (the
combination of electrical attraction and a concentration gradient) means
sodium REALLY "wants" to get in, if it could.
*Take a minute to draw a cell with several K+ leak channels, a few Na+
leak channels, and some Na+-K= exchange pumps. Draw an ion at each
of these channels, and draw an arrow to indicate which direction each
ion travels through. This will help you to visualize the uneven movement
of positive charges.
>C. Introduction to action potential generation/propagation, and release
of neurotransmitter
>>1. Local/graded potential- Neurotransmitters from the presynaptic cell
binds to receptors in the postsynaptic cell, causing chemically-gated Na+
channels to open, and Na + rushes in. The interior of the cell becomes
less negative, or depolarized (the voltage increases). If enough Na+ enters
that the voltage around the axon hillock reaches threshold (-60 - -55
mV), an action potential will be generated.
>>2. Action potential
>>>a. Voltage-regulated Na+ channels at the base of the axon (adjacent
to the hillock) respond to threshold voltage. At resting potential, the
activation gate of these channels is closed, while the inactivation gate is
open. At threshold, the activation gate opens. Now the channel is
completely open and Na+ ions enter the cell, following their
electrochemical gradient.
As Na+ enter, the voltage increases (becomes less negative). When voltage
reaches +30 mV, the inactivation gate closes, preventing further
movement by Na+. Inactivation gates will reopen when voltage returns to
around resting potential by the efflux of K+ (see below).
*Side note: Na+ continues to enter the cell even after the voltage has hit
zero because a concentration gradient for Na+ still exists. That is, even
though the total charges have been balanced, there are still more Na+
outside than inside the cell, so Na+ will continue to move down its
concentration gradient.
>>>b. Around the same time (+30mV), voltage-regulated K+ channels
open. K+ then rushes out, following its electrochemical gradient.
(Remember that there are more K+ inside than outside the cell, and at
+30 mV, the exterior of the cell is actually negative compared with the
interior). We are now in a phase where voltage is being restored by K+:
repolarization.
>>>c. When enough K+ have left the cell that the voltage hits -70 again,
K+ channels start to close, but some K+ still sneak through and voltage
will peak around -90mV. At this point the cell is hyperpolarized. A
hyperpolarized cell is less sensitive to stimuli, because a larger change in
voltage is required to hit threshold.
>>>d. Sodium-Potassium exchange pumps will return the cell to its
normal ion concentrations.
*Keep in mind that each of these changes in voltage is a local event; that
is, depolarization occurs first at the base of the axon. It causes an influx
of Na+ through neighboring channels. That influx affects neighboring
channels, which open; that effects the next neighbors down, and so-on.
So depolarization (and all subsequent events) occurs sequentially down
the axon, toward the synaptic terminals.
>>>e. Absolute refractory period: From the time the Na+ activation gate
opens until the time the INactivation gate reopens, the cell cannot fire
another action potential.
>>>>Relative refractory period: After the inactivation gate reopens until
the cell has restored resting ion distributions. This is the period of
hyperpolarization. The cell CAN fire another action potential during this
time… but it needs a stronger impulse to do so; why would that be?
>>3. An action potential reaches a synaptic terminal
>>>Voltage-gated Ca++ channels in the membrane open, Ca++ pours in
from the extracellular fluid.
>>>Ca++ triggers the release of Nt (neurotransmitters) from synaptic
vesicles
>>>Ca++ is actively pumped back out, and Nt will be either: 1)
reabsorbed by the presynaptic cell (ex, serotonin) or 2) first broken down
by enzymes in the synaptic cleft, then the remnants will be reabsorbed
by the presynaptic cell (ex, acetylcholine).
D. Speed of AP conduction (how fast an Action Potential travels down an
axon) affected by two factors
>>1. Diameter of axon- larger diameter = faster
>>2. Myelination- myelinated axons = faster. In a myelinated axon, only
the nodes of Ranvier contain ion channels, so the movement of ions
seems to "jump" from node to node. This type of conduction is called
saltatory (saltation- jumping).
*Conduction in non-myelinated axons called continuous
>>3. Axon types based on diameter & myelination
>>>>Type A- large, myelin; up to ~300mph; ex. motor fibers to skeletal
muscle
>>>>Type B- medium, myelin; up to ~40 mph; ex. some fibers to smooth
muscle, some from sensory
>>>>Type C- small, no myelin; ~2 mph; ex. many sensory, many
interneurons, some motor to smooth muscle