3. I. Stimulus:
• Are environmental energies that activate a specific body receptor.
• Include such as touch, pressure, sound, electrical, light, chemicals, and
temperature, change in pH, blood glucose, blood pressure…….
3
2. Receptor
• Are stimulus transducers that converts a particular form of environment energy into
receptor potential and then into action potentials in neurons.
• Every form of environment energy has its own specific receptors (receptor
specificity).
• Can be a sensory neuron or a specialized cell)
Ch-2 Excitable cells & membrane potentials
5. 5
Type of receptors
✓ Mechanoreceptors: detect deformation and sounds/motion. E.g. baroreceptors
✓ Thermoreceptor: detect temperature.
✓ Photoreceptors : detect visible light (390-670nm)
includes: cones & rods
✓ Chemoreceptors: receptors which detect chemical stimuli
e.g. olfactory & Gustatory receptors
✓ Nociceptors: detect pain stimuli ( AP Via free nerve endings + A-delta fibers)
✓ Osmorecepters: detect change in plasma osmolality
.
.
Ch-2 Excitable cells & membrane potentials
6. A basic model for the translation of an environmental stimulus into a perception...
6
Ch-2 Excitable cells & membrane potentials
7. Sensory receptors:
are specialized to transduce a particular type of stimulus energy into electrical signals.
7
Ch-2 Excitable cells & membrane potentials
8. Energy transduction
• ~ is a process in which the environmental stimulus energy is detected, transformed
into electrical signal, amplified & conducted to CNS.
Energy transduction requires:
✓ Unique stimulus that activates a specific receptor.
➢ The stimulus for which the receptor has the lowest threshold
(i.e. the lowest stimulus intensity that can be reliably detected).
✓ Unique receptor: each receptor is specialized to receive a particular type of stimulus.
➢ specific stimulus cation channel, usually Na+
8
Ch-2 Excitable cells & membrane potentials
9. a. Long receptor: when a primary sensory cell act as a receptor. e.g. olfactory nerve
9
Ch-2 Excitable cells & membrane potentials
10. b. Short receptor: when a special epithelial cells act as a receptor: secondary sensory cell.
E.g. gustatory cells 10
Ch-2 Excitable cells & membrane potentials
11. Stimulation of an afferent neuron with a receptor ending
11
Ch-2 Excitable cells & membrane potentials
Strength of stimuli
12. 12
Threshold Potential
✓ Minimum value of Em at which an action potential will occur 50%
of the time.
✓Initiated by rapid opening of fast Na+ channels.
✓Magnitude is 15mV (R=10-20mV) (-70mV → -55mV).
Strength of stimuli
• Sub threshold stimulus
• Threshold stimulus*
• Supra threshold stimulus
Ch-2 Excitable cells & membrane potentials
14. 14
Rationale of “Threshold Potential”
❖ Small random variations in Em are not misinterpreted as meaningful information
Ch-2 Excitable cells & membrane potentials
15. • Excitable cell: a cell which has a potential of producing an electrical signal in
response to the stimulus.
What is Excitable cell?
15
• Includes neurons & muscle cells .
Ch-2 Excitable cells & membrane potentials
16. ✓ Structural and functional unit of the nervous system.
✓ A neuron has four Structural & functional components:
a. Soma/cell body: metabolic center & input function
b. Dendrites: information reception function (input component)
c. Axon (axon Hillock): has integration, trigger & conductile function
d. Presynaptic terminals: store neurotransmitters (out put component)
The Neuron
16
✓ Each region has distinct role in generating signals + communicating with other nerve cells.
Ch-2 Excitable cells & membrane potentials
17. a. The soma (= cell body, perikaryon)
i. Gives rise to axon & dendrites.
ii. Has nucleus, nucleolus, mitochondria
+ RER + prominent GA.
iii. Origin of cytoskeletal elements:
a) Microtubules
b) Neurofilaments
c) Microfilaments
17
iv. Functions:
a. Metabolic center of the neuron
- Membrane constituents bound organelle (synthesize enzymes, neurotransmitters
& neuropeptides.
b. Reception and integration of incoming signals
Ch-2 Excitable cells & membrane potentials
19. c. Axon
i. Origin: soma, 0.1mm-2m long, ONLY ONE/neuron,
uniform dm. (θ = 0.2-20 μm).
ii. Special features:
• Axon hillock + axon collaterals (rare)
• Myelin sheath (+ axolemma + axoplasm ).
• Nodes of Ranvier
19
Ch-2 Excitable cells & membrane potentials
20. iii. Functions
a. Initiation of action potential at the axon hillock.
High density of voltage-gated ion channels of Na+, K+, Ca2+→
threshold (-45mv)
b. Impulse conduction: action potential (100mV, 1-100m/s)
c. Axonal transport (anterograde+ retrograde)
20
Ch-2 Excitable cells & membrane potentials
21. c. Axoplasmic Transport
i. Occurs in the microtubules, ATP and Ca2+ dependent.
ii. Purpose: replenishment of synaptic vesicles & enzymes responsible for NTs.
iii. Bidirectional
21
Ch-2 Excitable cells & membrane potentials
22. 1. Anterograde: Soma/Cell body → Nerve terminal
• 2 types
i. Fast anterograde axonal transport
a. 400mm/day (= 40cm/day)
b. Membrane-bound organelles
+ mitochondria (+ vesicles).
c. Motor molecule is kinesin
22
ii. Slow anterograde axonal transport
a. 1mm/day (R= 0.2-2.5mm/day)
b. Soluble proteins, precursors (actins, tubulins…)
c. Not dependent on microtubule, No ATPase motor molecule.
Ch-2 Excitable cells & membrane potentials
24. 2. Retrograde: Soma/Cell body Nerve terminal
i. Fast retrograde axonal transport.
ii. Velocity = 200 - 300mm/d (= 20cm/d - 30cm/d)
iii. Motor Molecule is dynein.
iv. Returns synaptic vesicle membrane to the soma for lysosomal degradation
or recycling.
v. Permits communication between the synaptic terminal and the cell body.
24
Ch-2 Excitable cells & membrane potentials
25. Summary of axonal transport
25
Ch-2 Excitable cells & membrane potentials
26. d. Synaptic terminals/nerve terminals, synaptic boutons …
✓ Transmitting elements of the neuron, NT.
✓ Synaptic vesicles + high number of mitochondria.
➢ Cell sending out information → Presynaptic cell
➢ Cell receiving the information → Postsynaptic cell
✓ If termination of presynaptic neuron:
• On dendritic spine of postsynaptic neuron → Excitatory (90%).
• On cell body → Excitatory (10%)
✓ Principles of connectional specificity.
26
Ch-2 Excitable cells & membrane potentials
28. Membrane Potential
• Def/n: electrical energy difference between the inside & outside of the cell membrane.
• Membrane potential charge separation across the membrane.
Em = Vin – Vout, where
Vin = Potential on the inside of the cell
Vout = Potential on the outside
Em = Membrane potential (mV)
• All cells have resting membrane potentials (RMP).
• The Range of Em: -20 mV to -90mV (depends on the cell type).
28
Ch-2 Excitable cells & membrane potentials
29. 29
• Cells are polarized at rest (separation of charges at rest).
positive, outside of the cell membrane
negative, inside of the cell membrane
✓Resting membrane potential of a neuron
-70mV
Ch-2 Excitable cells & membrane potentials
30. I. Resting Membrane Potential (RMP)
✓ Steady transmembrane potential of a cell that is not producing an electrical signal.
✓ No net flow of ions across the plasma membrane.
(No net inward current), RMP
✓ Always negative in nerve & muscle cells.
✓ Magnitude (RMP, relatively) is κ for individual cell types.
o Nerve (-70 mV)
o cardiac (peacemaker cell (-60 to -45mV ) & CMC (-85mV)
o skeletal muscle: -90mV
o Smooth muscle: -55 to -30mV
• RMP is necessary for the cell to fire an action potential.
30
Ch-2 Excitable cells & membrane potentials
31. Resting membrane potential of a neuron
31
-70mV
✓ RMP is nearly equals to that of EK.
Ch-2 Excitable cells & membrane potentials
32. Determinants of membrane potential
I. Passive determinants
II. Active determinant
I. Passive Determinants
A. Biochemical nature of plasma membrane of the cell.
Lipid bilayer (7nm): Selective permeability.
polarized at rest: Separation of Charge
• Extracellular: +VE
• Intracellular: - VE
B. Asymmetrical/Unequal distribution
of ions across the membrane.
32
Ch-2 Excitable cells & membrane potentials
33. Concentration of ions
Electrostatic
Insi Outside [ ] gradient pressure
Sodium (Na+) 12mM 145mM into cell into cell
Potassium (K+) 150mM 5mM out of cell into cell
Chloride (Cl-) 9mM 125mM into out of
Calcium (Ca2+) 10-4mM 2.5mM into cell into cell
Organic anions: Fixed anions (Proteins, nucleotides, polyphosphates…)
33
Ch-2 Excitable cells & membrane potentials
34. C. Leakage (Leak, non-gated, passive, resting) channels
• Leak K+ channels, leak Na+ channels, leak Cl- channels
• Leakage K+ channels are open at resting potential more than Na+, Cl- channels .
• RMP is nearly equals to that of the EK.
34
-70mV
Ch-2 Excitable cells & membrane potentials
36. II. Active Determinant
A. Na+-K+-ATPase (Na+-K+ pump)
Features:
✓ A carrier molecule uses the membrane-bound ATPase.
✓ Primary active transport process (consumes ATP, pumps against concen. gradient).
✓ Operates as antiporter (coupled transporter):
➢ Pumping 3Na+ out of the cell
➢ Pumping 2K+ in (Electrogenic pump).
Functions:
✓ Maintenance of gradient of Na+ and K+ across the cellmembrane.
- Controls cell volume ( Na+ regulating osmotic forces)
- Control of membrane potential & excitability.
36
Ch-2 Excitable cells & membrane potentials
38. ✓ ΔEm: Basis of signaling in excitable cells (neurons, muscle cells).
Cell signaling
✓ It is a change in membrane potential in response to stimulus (RMP→RP).
✓
Reason:
✓ Due to the presence of high
density stimulus sensitive cation
ion channels in their cell
membrane.
38
Ch-2 Excitable cells & membrane potentials
39. Types of signaling
1. Graded potentials/Local potentials
2. Action potentials
Graded potentials:
Def.:- local changes in Em in either depolarizing or hyperpolarizing direction.
✓ Usually Na+ channels, which open in response to stimuli causing
Na+ to move into the cell (depolarization).
if Cl- .....moves into the cell/ or K+ moves out......Hyperpolarisation
✓ Serves as short distance signals.
• Initiates action potentials if threshold is reached
39
Ch-2 Excitable cells & membrane potentials
40. Features
1. Depolarizing or hyperpolarizing
2. Variable in amplitude and duration (AM)
3. Conducted decrementally
4. Can be summed (Temporal, Spatial)
5. Has no threshold
6. Has no refractory period
7. Propagation is passive
40
Ch-2 Excitable cells & membrane potentials
42. Stimulus (physical, mechanical, chemical, electrical…)
Sensory receptors
*Transform stimulus energy /Transduction
Ion channels open
Inward flow of current (Na+, K+)
Depolarization → ΔEm
Receptor potential /Generator potential
if > threshold P
Action Potential
CNS ...→ RESPONSE.
d. Mechanism of signaling
42
Ch-2 Excitable cells & membrane potentials
43. 2. Action Potentials
Def: rapid, transient, self-propagating electrical excitation in the plasma
membrane of excitable cells.
✓ Genesis/Initiation: electrical perturbation → ΔEm → AP.
✓ Sequential opening of voltage-gated channels of Na+ and K+.
✓ Sends signals over longer distances.
43
-70mV
Ch-2 Excitable cells & membrane potentials
44. 44
Conformations of voltage-gated sodium channels
Conformations of voltage-gated potassium channel
Ch-2 Excitable cells & membrane potentials
45. Features:
1. All-or-none phenomenon.
• Always be full sized.
• It will not get lost along the way.
• Rapid and reliable information.
2. Has threshold.
3. Amplitude and duration is κ
4. Always depolarizing.
5. Has refractory period.
6. Non-decremental.
7. Propagation is active.
45
Ch-2 Excitable cells & membrane potentials
46. • SAME SHAPE, AMPLITUDE + DURATION in same excitable cells.
• Shape, amplitude and duration of AP is different in different excitable cells.
46
Ch-2 Excitable cells & membrane potentials
47. Refractoriness/Refractory period
Def. an interval during which it is more difficult to elicit an AP.
(∵ voltage and time-dependent nature of gating particles) .
Types
a. Absolute refractory period
b. Relative refractory period
47
Ch-2 Excitable cells & membrane potentials
48. a. Absolute Refractory Period:
• Another AP can not be elicited, regardless of the strength of the stimulus.
b. Relative Refractory Period
• A second AP can be elicited if the stimulus is adequate.
• Stimulus must be greater than normal (suprathreshold)
Rationale of Refractoriness: faithfulness!
✓ Ensures ONLY one-way of propagation of APs along an axon.
✓ Imposes a limit on the maximum rate a neuron can fire.
✓ Prevents APs from summating.
48
Ch-2 Excitable cells & membrane potentials
52. 52
Synaptic transmission
✓ A site at which an impulse is transmitted from one cell to another.
Pre-synaptic--- A neuron terminal at which a impulse/
neurotransmitter is transmitted from.
Post-synaptic--- A neuron’s at which an impulse/
neurotransmitter transmitted to.
Ch-2 Excitable cells & membrane potentials
53. 53
✓ Neuronal communication begins with the stimulation of a neuron.
✓ One neuron may be stimulated by another, by a receptor cell, or even
by some physical event such as pressure, pain, temperature…...
✓ Such neurons are sensory neurons and they provide information to
the CNS about both the internal & external environments .
✓ Neurons: specialized cells for communication.
Types:
i. Sensory neuron ….send sensory info to CNS
ii. Interneuron…integrate the information and then send
commands to motor neurons
iii. Motor neuron…synapse with effectors (muscles or glands)
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54. 54
There are two types of
1. Electrical synapses
✓ AΔEm in one cell is transmitted to the other cell by the direct flow
of current (cytoplasmic bridge/ gap junction between cells).
✓ No synaptic delay (direct interactions between neighboring cells).
✓ Chemical messenger (neurotransmitter) is released from a neuron
into the synaptic cleft.
✓ Neurotransmitter in the synaptic cleft binds to a receptor on the
post-synaptic cell.
2. chemical synapses
Ch-2 Excitable cells & membrane potentials
56. 56
Sequence of events at chemical synapses:
Action potential in presynaptic cell
↓
Depolarization of plasma membrane of the presynaptic axon terminal
↓
Entry of Ca2+ into presynaptic terminal
↓
Fusion of membranes & release of the transmitter by the presynaptic terminal
↓
Chemical combination of the transmitter with specific receptors in
the plasma membrane of the postsynaptic cell
↓
Transient change in the conductance of the postsynaptic plasma membrane to specific ions.
↓
Transient change in the Em of the postsynaptic cell
Ch-2 Excitable cells & membrane potentials
57. 57
Sequence of events at chemical synapses EPSP
Ch-2 Excitable cells & membrane potentials
