BIO 3520 Notes, 9/05/08
NEUROPHYSIOLOGY I
I. Introduction. [Widmaier, pp. 137-139]
A. Nervous tissue is specialized for initiation and conduction of electrical
signals (nerve impulses).
B. Functions of the nervous system.
1. Sensation.
2. Communication.
3. Control.
C. History of the neuron theory.
1. Neuron theory proposed that the nervous system was not a
continuous web of tissue, but composed of individual cells called
neurons.
2. Camillo Golgi (1870's) developed the stains necessary to visualize
the fine structure of the nervous system.
3. Santiago Ramon y Cajal (1891) used Golgi's stain to show that
nerve cells were not physically interconnected (figure).
a. Established the neuron theory.
D. Neurons.
1. Functional unit of the nervous system.
2. Anatomy of the neuron (fig. 6-1, figure).
a. Cell body -- contains nucleus and organelles.
b. Dendrites.
1. Series of highly branched outgrowths from cell body.
2. Carry nerve impulses toward the cell body.
3. Increase the receptive surface of neuron.
c. Axon (nerve fiber).
1. Single process extending from cell body.
2. Carries nerve impulses away from the cell body.
3. Axon hillock -- site of initiation of action potential.
4. Axon terminal -- site of communication with other cells.
5. Many axons are wrapped in a fatty material -- myelin sheath
(fig. 6-2).
a. Insulation.
b. Speeds conduction.
II. Principles of Electrical Conduction. [pg. 144]
A. Discovery of "animal electricity".
1. Luigi Galvani (1780's) demonstrated that the stimulus for muscle
contraction was electrical.
B. Electricity is the flow of electrons from an area of high concentration to
an area of low concentration.
C. The rate of flow (current) depends on the electrical potential difference
(voltage) and resistance to flow.
Ohm's law: I = V / R
1. Materials with a high degree of resistance are insulators.
2. Materials with a low degree of resistance are conductors.
III. Resting Membrane Potential. [pp. 144-149]
A. Resting membrane potential = Membrane potential of an unstimulated cell.
1. It is usually about -70 mV (fig. 6-8).
B. Maintenance of the resting membrane potential depends on:
1. Selective permeability of the cell membrane.
a. Permeable to K+.
b. Relatively impermeable to Na+.
c. Impermeable to proteins.
2. Maintenance of ion gradients by the Na-K pump (fig. 6-13).
C. Calculation of the membrane potential (VM) -- Goldman equation.
1. Case 1: Suppose that K+ is the only diffusible ion.
a. VM is expressed by the Nernst equation for K+.
2. Case 2: Suppose that Na+ is also diffusible.
a. VM is somewhere between the equilibrium potentials for Na+ and K+.
3. Case 3: Add Cl- to the equation (Note: Cl- has a valence of -1).
VM = 60 log PK [K+]o + PNa [Na+]o + PCl [Cl-]i
PK [K+]i + PNa [Na+]i + PCl [Cl-]o
4. The membrane potential is a composite of the equilibrium potentials
and relative permeabilities of the most prevalent ions.
5. Relative permeabilities:
PK > PCl > PNa 50 :10:1
6. Solve Goldman equation:
7. The more permeable the membrane is to an ion, the closer VM will be
to the equilibrium potential of that ion (fig. 6-12).
8. Problem: What happens to the membrane potential if PNa increases
from 1 to 600?
IV. Graded Potentials. [pp. 149-152]
A. Changes in membrane potential result from changes in membrane
permeability in response to a stimulus.
1. At rest, membrane is polarized (-70 mV).
2. Depolarization = Increase in the membrane potential towards zero
(i.e. less negative) (fig. 6-14).
3. Repolarization = Return from the depolarized state towards the
resting membrane potential (i.e. more negative).
4. Hyperpolarization = Decrease in the membrane potential below
the resting membrane potential.
B. Graded potential = Local change in membrane potential in either a
depolarizing or hyperpolarizing direction.
C. Properties (fig. 6-16).
1. Can be depolarizing or hyperpolarizing.
2. Can vary in amplitude.
a. Related to the intensity of the stimulus.
3. Cannot be transmitted over long distances.
a. Magnitude of potential change decreases with distance away from
the site of stimulation.
b. Graded potential will die out within a few millimeters.
4. Can be summed in time and space.
a. Temporal summation.
b. Spatial summation.
VI. Action Potential. [pp. 151-158]
A. Certain cells have excitable membranes (ex. nerve and muscle).
1. Excitable membrane = Cell membrane capable of producing or
conducting electrical impulses.
B. Action potential = Rapid, transient reversal of the polarity of the
membrane potential.
C. Alan Hodgkin and Andrew Huxley.
1. Intracellular recording of changes in membrane potential of a single
squid axon during action potential (1939).
2. Voltage clamp experiments.
a. Electronic circuitry is used to set the membrane potential at some
voltage and hold it there (voltage clamp).
b. Measure flow of ions (conductance) at that voltage (figure).
3. Developed ionic hypothesis of the action potential (late 1940's).
D. Ionic hypothesis of the action potential .
1. Explains the action potential in terms of the movement of ions
across the cell membrane.
2. Membranes contain channels through which Na+ or K+ may pass
(fig. 6-18).
a. Na+ channels are usually closed, K+ partly open.
3. Rising phase.
a. Membrane depolarization due to a stimulus causes some
voltage-gated Na+ channels open ----> increase Na+ permeability.
b. Na+ diffuses into cell ----> depolarization.
c. Depolarization causes more Na+ channels to open.
d. Positive feedback loop (fig. 6-20a).
d. Relate to Goldman equation.
e. After opening, Na+ channels rapidly close and are inactivated.
4. Falling phase.
a. Voltage-gated K+ channels open ----> increased PK.
b. K+ leaves cell ----> repolarization.
c. K+ channels remain open as long as the membrane is depolarized
(fig. 6-20b).
5. Hyperpolarization.
a. Continuation of falling phase -- K+ channels begin to close.
b. Membrane potential approaches K+ equilibrium potential.
6. Review permeability changes (fig. 6-19b).
a. Na+ and K+ concentration gradients are maintained by the
Na-K pump.
E. Drugs that alter ion channels.
1. Tetrodotoxin -- from Japanese puffer fish.
a. Blocks Na+ channels ---->
2. Local anesthetics (ex. xylocaine).
a. Block Na+ channels (not as potent as tetrodotoxin).
3. Tetraethylammonium (TEA).
a. Blocks K+ channels ---->
F. Properties of the action potential (table 6-7).
1. Only depolarizing.
2. All-or-none.
a. Threshold = Minimum stimulus required to produce an action
potential (about -55 mV).
b. Once threshold is reached, action potential is always the same
amplitude.
3. Refractory period (figure).
a. Membrane becomes refractory (unresponsive) to a second
stimulus.
b. Absolute refractory period = Period of time following an
action potential during which a second action potential cannot be
produced.
1. Lasts a few msec.
2. Due to inactivation of Na+ channels (fig. 6-18).
c. Relative refractory period = Period of time following an action
potential during which a larger than normal stimulus is required
to trigger a second action potential.
1. Lasts several msec.
2. K+ channels are open.
3. Membrane is hyperpolarized.
4. Can be transmitted over long distances.
a. Magnitude of potential change is maintained with distance away
from the site of stimulation.
b. Current flows from one area of the membrane to the next,
triggering action potentials as it goes (fig. 6-22).
c. Wave of depolarization is followed by a wave of repolarization
(figure).
d. Allows action potentials to be propagated unchanged along nerve
fibers up to 1 m long.
G. Velocity of nerve conduction.
1. Factors contributing to fast conduction.
a. Large diameter.
b. Myelination (fig. 6-2).
1. Gaps in myelin sheath -- nodes of Ranvier (fig. 6-23).
2. High density of voltage-gated ion channels in nodes.
3. Saltatory conduction.
4. Conserves energy.
2. Small, unmyelinated fibers are slowest (0.5 m/sec).
3. Large, myelinated fibers are fastest (100 m/sec).
4. Multiple sclerosis.
a. Inflammation or destruction of myelin sheath (figure).
b. Results in improper conduction of nerve impulses due to
damaged myelin sheath.
c. Occurs most commonly in young adults, especially women.
d. Symptoms include muscle weakness, uncoordination, visual
disturbances, and paralysis.
VII. Synaptic Transmission. [pp. 159-171]
A. Discovery of the first neurotransmitter.
1. Classic experiment of Otto Loewi (1920).
2. First direct evidence of chemical transmission of a neuronal signal.
3. Discovery of the first neurotransmitter -- acetylcholine.
B. Neurotransmitter = Chemical messenger released by a neuron.
C. Synapse = Specialized junction between a neuron and another cell
across which nerve impulses are transmitted (fig. 6-25).
1. Presynaptic neuron -- sends signal.
2. Postsynaptic neuron -- receives signal.
3. Synaptic cleft -- small space between the two neurons.
4. Synaptic vesicles in presynaptic axon terminal --
store neurotransmitters.
5. Neurotransmitter receptors on postsynaptic membrane.
D. Mechanism of synaptic transmission (fig. 6-27).
1. Action potential reaches axon terminal of presynaptic neuron.
2. Causes opening of voltage-gated Ca++ channels in the presynaptic
cell membrane.
3. Increased cytoplasmic Ca++ causes some synaptic vesicles to
release their contents into the synaptic cleft by exocytosis.
4. Neurotransmitters diffuse across synaptic cleft and bind to receptors
on postsynaptic nerve cell membrane.
5. Binding of neurotransmitters to receptors causes a change in the
membrane potential.
a. Changes in membrane potential are due to changes in ion
permeability.
b. Depolarization ----> excitatory postsynaptic potential (EPSP).
1. Due to opening of ligand-gated Na+ channels.
c. Hyperpolarization ----> inhibitory postsynaptic potential (IPSP).
1. Due to opening of ligand-gated K+ or Cl- channels.
6. Postsynaptic potentials are graded potentials ----> can be summed.
a. If sum of EPSP's (minus IPSP's) arriving at the axon hillock reaches
threshold ----> action potential (fig. 6-31, figure).
E. Synaptic delay.
1. Communication between neurons takes time (up to 1 msec).
2. Pathways involving more synapses are slower.
F. Examples of neurotransmitters.
1. Acetylcholine.
a. Slows the heart.
b. Skeletal muscle contraction.
c. Cognitive function and memory.
d. Destruction of ACh-containing neurons associated with
Alzheimer's disease.
2. Amines (fig. 6-35).
a. Norepinephrine.
1. Behavioral arousal.
b. Dopamine.
1. Pleasure and reward.
2. Cocaine and other drugs of abuse increase dopamine levels
in brain.
3. Coordination of movement.
4. Parkinson's disease -- Destruction of dopamine-containing
neurons in an area of the brain concerned with movement.
a. Symptoms -- tremor and rigidity.
b. Treatment -- L-dopa ----> converted to dopamine in CNS.
c. Serotonin.
1. Regulation of mood.
2. Levels may be too low in certain forms of mental illness
(ex. depression).
3. Antidepressant drugs like Prozac increase serotonin levels
in brain.
3. Amino acids.
a. Glutamate -- excitatory.
b. Glycine -- inhibitory.
4. Peptides.
a. Enkephalin -- modulation of pain pathways.
5. Gases.
a. Nitric oxide.
1. Dilates blood vessels ----> increases blood flow to organ.
2. Viagra increases effectiveness of nitric oxide ----> treatment
of erectile dysfunction.
G. Termination of neurotransmitter action (fig. 6-34, figure).
1. Diffusion -- free neurotransmitters diffuse away from synaptic cleft ---->
receptor-bound neurotransmitters dissociate as the concentration falls.
2.
3.