1. Physiology of a Neuron From Dendrite to synaptic transmission1

2. Outline Dendrites A. Graded potentials i. EPSP ii. IPSP
B. Summation- temporal and spatial
Axon
A. Action potentials
B. Refractory periods
C. Myelination
Synapse
A. Voltage gated calcium channels
B. Neurotransmitters
IV. Functional classification of receptors
A. Ionotropic
B. Metabotropic
i. Second messengers
V. Drugs that induce spastic or flaccid paralysis

3. Neuron anatomy Draw and label a neuron
Dendrite - projections from the soma
the sensory portion of the neuron
Soma - main body of the neuron
Axon hillock- trigger zone
Axon - extends from soma to the terminal
the effector part of the neuron
Terminal bouton/ axonal terminus/synaptic terminal
Synaptic vesicles
Synaptic cleft 3

4. Function of Dendrites in Stimulating Neurons
Dendrites spaced in all directions from neuronal soma.
allows signal reception from a large spatial area providing the opportunity for summation of signals from many presynaptic neurons
Dendrites transmit signals by graded local potentials from opening of LGC’s
LGC (Ligand-gated channels): are not dependent on membrane potential but binding of ligands (e.g. neurotransmitters)‏
Neurotransmitter receptors
Located on dendrites and cell body
Intensity of potential diffuses away from stimulus
Axon
hillock
VGC’s
LGC’s
Act as receptor for neurotransmitter
open and allow ligand in or out of cell 4 4

5. Types of Ligand Gated Channels (LGC’s)‏
Pore loop- amino acids here control ion selectivity, what passes
Gene Families- many different channel genes and have different structures, functions and expression patterns
Importance is found in diversity- many human diseases are associated with dysfunction of individual classes of ion channels
Na+ LGC K+ LGC Cl- LGC
Vm -74 mV
What would happen to the resting membrane potential if these channels opened?

6. -45mV axon dendrite 14 mEq/L K+ : 4.5 mEq/L 120 mEq/L Cl- : 107 mEq/L
The Excitatory Postsynaptic Potential (EPSP)‏
Na+ ions rush to inside of membrane through ionophores opened by transmitter.
The increase in voltage above the normal resting potential (to a less negative value is the excitatory postsynaptic potential.
A single EPSP can be mV (how many mV difference do we need to reach threshold?
axon
dendrite
Na+: 142 mEq/L
14 mEq/L
K+ : 4.5 mEq/L
120 mEq/L
Cl- : 107 mEq/L
8 mEq/L
-45mV
Membrane is depolarized, more likely to reach threshold 6 6

7. -90mV The Inhibitory Postsynaptic Potential (IPSP) K+ : 4.5 mEq/L axon
Inhibitory synapses open K+ or Cl- channels and causes hyperpolarization of the neuron. Making neuron less likely to reach threshold
Positively charged K+ ions moving to exterior make membrane potential more negative than normal (hyperpolarizing).
Negatively charged Cl- ions moving to interior make membrane potential more negative than usual (hyperpolarizing).
axon
Na+: 142 mEq/L
14 mEq/L
K+ : 4.5 mEq/L
120 mEq/L
Cl- : 107 mEq/L
8 mEq/L
-90mV 7 7

8. Whether a neuron “responds” or not, depends on temporal and spatial summation of EPSPs and IPSPs
These channels open and close rapidly providing a means for rapid activation or rapid inhibition of postsynaptic neurons.
1msec is needed for an action potential, but a graded potential can last ~15msec. This means we can “add” excitatory and inhibitory potentials
Temporal summation: same presynaptic neuron fires repeatedly 8 8

9. Spatial summation- stimuli from two different presynaptic neurons (different locations)9 9

10. Disturbing an Excitable Cell
Electrical stimulation (or even mechanical stimulation) can result in changes in voltage. Depolarizing currents change the voltage on the membrane, bringing it toward threshold:
If stimuli are sub-threshold, the result is a local potential
If stimuli are threshold or above threshold stimuli, the result is an action potential 10

11. What happens at threshold?
A temporary, short-lived membrane permeability change. Membrane becomes 40 x more permeable to Na+ than to K+, then quickly returns to previous state
How?
Opening and closing of voltage-gated channels. VGC (Voltage-gated channels): Open/close depending on the voltage across the membrane
Na+ VGC, K+ VGC, Ca++VGC
Located on the axon, at hillock and beyond
Can allow ions to move at high rates
Allow ions to move down their EC gradients
Conductances are voltage dependent
Threshold is the “trigger” that starts a “dance of the gates” 11

12. The action potential, dance of the gates
Upstroke
Na+ permeability increases
Membrane potential approaches E Na+
Downstroke
Potassium permeability increases
Hyperpolarization occurs due to increased K+ conductance from late K+VGC closure
Membrane potential approaches E K+ 12

13. 13

14. but it also causes inactivation
Ion channels – Activation, Inactivation, deactivation
Depolarization causes:
Na channels to activate (open)‏
but it also causes inactivation
inactivated channels do not pass any ions (non-conducting state)‏
By contrast, most K channels show activation and deactivation but not inactivation
The fall in current at the end is deactivation (opposite of activation)‏
open
inactivation
inactivated
closed
depolarization
repolarization 14
Copyright © 2006 by Elsevier, Inc. 14

15. Refractory Periods ARP - due to voltage inactivation of Na channelsmV
-40
-80
Threshold
msec
Maximum frequency is several hundred APs per second.
Absolute
Relative
ARP - due to voltage inactivation of Na channels
Refractory periods limit maximum frequency of APs 15 15

16. Functions of action potentials
Information delivery to CNS
Transfers all sensory input to CNS.
The frequency of APs encodes information (recall amplitude cannot change).
Rapid transmission over distance (nerve cell APs)‏
Note: speed depends on fiber size and whether it is myelinated.
In non-nervous tissue APs are the initiators of a range of cellular responses.
Muscle contraction 16
Figure 5-16; Guyton & Hall 16

17. A “wave of depolarization” occurs along the neighboring areas.
matthews/actionp.html
Figure 5-17; Guyton & Hall
Saltatory Conduction
The AP is a passive event: ions diffuse down their EC gradients when gated channels open.
A “wave of depolarization” occurs along the neighboring areas.
Occurs in one direction along the axon; actually, AP regenerates over and over, at each point by diffusion of incoming Na+ ….WHY?
Refractory period (Na+ channels become inactivated).
AP’s only occur at the nodes (Na channels concentrated here!)‏
increased velocity
energy conservation 17 17

18. - non-myelinated vs myelinated -
Conduction velocity
- non-myelinated vs myelinated -
non-myelinated
myelinated 18 18

19. Multiple Sclerosis
- MS is an immune-mediated inflammatory demyelinating disease of the CNS -
Patients have a difficult time describing their symptoms. Patients may present with paresthesias of a hand that resolves, followed in a couple of months by weakness in a leg or visual disturbances. Patients frequently do not bring these complaints to their doctors because they resolve. Eventually, the resolution of the neurologic deficits is incomplete or their occurrence is too frequent, and the diagnostic dilemma begins.
- About 1 person per 1000 in US is thought to have the disease - The female-to-male ratio is 2:1 - whites of northern European descent have the highest incidence 19
Copyright © 2006 by Elsevier, Inc. 19

20. The Synapse Structures important to the function of the synapse:
presynaptic vesicles
contain neurotransmitter substances to excite or inhibit postsynaptic neuron
mitochondria
provide energy to synthesize neurotransmitter
Membrane depolarization by an action potential causes emptying of a small number of vesicles into the synaptic cleft
Presynaptic membranes contain voltage - gated calcium channels.
depolarization of the presynaptic membrane by an action potential opens Ca2+ channels
influx of Ca2+ induces the release of the neurotransmitter substance
The Synapse
VOCC
Ca+2
Postsynaptic membrane contains receptor proteins for the transmitter released from the presynaptic terminal. 20 20

21. Synaptic Events-watch animation
NTS release
NTS diffuses across cleft
Binds to receptors (LGC’s) reversible binding
Opens LGC (LGC’s are ion selective) and diffusion of ions: Influx or efflux
Allowing depolarization or hyperpolarization of cell body
Result in graded voltage changes, local potentials in postsynaptic cell body
If depolarizing, called EPSP
If hyperpolarizing, called IPSP 21