1. Neurophysiology NEUROTRANSMISSION
Chapter 12

2. Chemical Synapse Vocabulary
Presynaptic neuron
Postsynaptic neuron
Synapse – means of communication between each neuron and the next cell; space
Excitatory neurotransmitters – chemicals that cause nerve impulses (e.g. ACh, glutamate)
Inhibitory neurotransmitters – chemicals that inhibit nerve impulses (e.g.gama aminobutyric acid – GABA)
We focus on chemical synapse; electrical synapse is rare (CNS & PNS); no neurotransmitters, presynaptic and postsynaptic neurons are very close together - less than 2 nm and action potential can move quickly from one cell to another without neurotransmitters
Neuromodulators (such as endorphins – pain relief) influence neuotransmitters’ release

3. Steps of Synaptic Transmission
Step 1: Action potential arrives at the axon terminal
Step 2: Release of neurotransmitter from a vesicle
Step 3: Neurotransmitter binds to receptor site on ion channel on postsynaptic neuron
Step 4: Ions cross the membrane through open channels
Step 5: The influx of ions causes action potential in postsynaptic neuron (details are coming up - )
Step 6: Removal of neurotransmitter

4. Major Neurotransmitters in the Body
Acetylcholine – regulates muscles and memory; mostly excitatory
Dopamine – produces feelings of pleasure; mostly inhibitory
GABA – major inhibitory neurotransmitter in the brain
Glutamate - major excitatory neurotransmitter in the brain
Seratonin – involved in many functions including mood, appetite, and sensory perception; inhibitory in pain pathways
Norephinephrine – regulates normal brain processes and is a part of the fight-or-flight response; usually excitatory
Norephinephrine is also a hormone
Depression and suicidal tendencies – imbalance of seratonin
Lack of Ach – Alzheimer’s
Lack of dopamine – Parkinson’s disease (lack of inhibitory control leads to overstimulation of skeletal muscles – rigidity and stiffness)
Many antidepressants – inhibit reabsorption of seratonin, over time this may relieve symptoms
Interactions among seratonin and norephinephrine may be involved in regulation of sleep & wake cycle

5. Resting Membrane Potential (RMP)
The outside of the cell is more positive (Na+) than the inside (K+)
Electrical charge gradient associated with the cell membrane; typically -70 millivolts

6. Protein Channels
Ion protein channels are chemically, mechanically or voltage regulated
Ion channels open in response to the particular stimulus and allow ions to flow in or out the cell
Flow of ions changes the membrane potential/voltage
Sudden change in membrane potential that accompanies activity = action potential (nerve impulse)

7. A Special Ion Channel: Na+/K+ ATPase
When a neuron is at rest, there is a slow leakage of Na+ into the cell & K+ out of the cell (along concentration gradient)
Na+/K+ ATPase pumps 3 Na+ out and 2 K+ in per ATP hydrolysis & thus prevents reaching equilibrium of Na+ & K+ ions

8. Steps of Action Potential
Step 1: Resting
Step 2: Depolarization
Step 3: Repolarization
Step 4: Return to normal permeability

9. Step 1: Resting (-70 mV) Step 2: Depolarization
Neurotransmitters bind to their receptors on a postsynaptic neuron, chemically gated Na+ channels open, Na+ flows in, and local potential reaches a threshold limit (-55mV)
Then, voltage-gated Na+ channels open and Na+ ions rush into the cell
Membrane potential reaches +30 mV
Local Potential = graded potential (due to the binding of neurotransmitter and influx of ions), not long distance signal

10. Step 3: Repolarization
Na+ channels close when the inside of the axon becomes sufficiently positive (30 mV)
Voltage-regulated K+ channels open & K+ flows out

11. Step 4: Return to resting potential
Ion movements drive the membrane potential back toward resting membrane potential value
Na+/K+ ATPase continues pumping ions, adjusting levels back to resting equilibrium levels
Hyperpolarization - briefly the exterior of the membrane is more negative than resting potential voltage level
Refractory period - the time during which a nerve cell cannot generate another action potential despite stimulation
Refractory period occurs because the voltage-gated Na+ channels must be reset before they can respond to the next stimulus

12. And Another Look www.blackwellpublishing.com/matthews/channel.html
instead, a “jumping” depolarization
Saltatory Propagation of Action Potential: myelinated axons transmit an Action Potential differently
the myelin sheath acts as an insulator preventing ion flows in and out of the membrane
neurofibral nodes (node of Ranvier) interrupt the myelin sheath and permit ion flows at the exposed locations on the axon membrane
the nodes contain a high density of voltage-gated Na+ channels

13. Closer Look at Action Potential