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THE GRADED POTENTIAL & THE ACTION POTENTIAL

Ginus Partadiredja Department of Physiology Faculty of Medicine GMU

Learning Objectives

1. To understand basic concepts related to graded potentials

2. To understand basic concepts related to action potentials 3. To understand the differences between graded potentials and action potentials

 Neuron: Functional unit of nervous system, with

excitability and conductivity characteristics The number of neurons in the CNS = 1011 = 10 billion Glial cells (neuroglia): Non conductive cells which protect, maintain, and support the nervous system The number of glial cells = 10 50 x of neurons

THE HISTOLOGY OF NEURON

Dendrite Cell body/ soma Axon hillock Axon

Myelin sheath
Synaptic knobs/ terminal buttons/

axon telodendria

Pyramidal (pseudounipolar)

 Dendrites & soma receptive segment Axon closest to axon hillock initial segment Axon conductive segment Axon terminal transmissive segment

 Stimulus: Any change in the environment that is strong enough to initiate an action potential Action potential: An electrical signal that propagates along the surface of the membrane of a neuron Graded potential: A small deviation from the resting membrane potential that occurs because ligand-gated or mechanically gated channels open or close hyperpolarizing or depolarizing graded potential Receptor potential (sensory receptors) Post-synaptic potential (mainly in dendrites & soma): Excitatory post-synaptic potential (EPSP) Inhibitory post-synaptic potential (IPSP)

 Action potential generator potential/ receptor potential Receptor - sensory receptor - proteins bind to hormones/ neurotransmitters Sensory receptors: Transducers which alter various energy in the environment into action potentials in neurons Sensory organs = receptor + non neural cells

 Mechanism:
Stimulus receptor/ generator potential (EPSP like; does not spread, graded, local) reach firing level/ neuronal threshold action potential

THE PHYSIOLOGY OF NEURON

Recording with an electrode inside an axon resting membrane potential/ polarization typically -70 mV (the potential difference between the inside and outside of the axon, the inside being more negative than the extra-cellular fluid)

 Resting membrane potential small build-up of negative ions along the inside of membrane, and positive ions along the outside Neurons range: -40 to -90 mV (ranges of membrane potential of cells: +5mV to -100 mV)

Resting membrane potential

 ECF Na+ and Cl ICF K+ and phosphates (attached to ATP and amino acids) Factors causing the negativity inside neurons: 1. Leakage of K+ to ECF (K+ channels > Na+ channels)

2. Negative ions inside neurons cannot leave cells

(attached to ATP, proteins, or larger molecules) 3. Na+/K+ ATPase pumps (3 Na+ out for 2 K+ in) contributes only -3 mV

 Threshold stimulus: a stimulus which is strong enough to

depolarize the membrane to threshold

Subthreshold stimulus; suprathreshold stimulus Firing level/ threshold: The point where depolarization accelerates (following the increase by 15 mV)

 Na+ channels open Na+ enters the cell

 Depolarization: The reversal of potential membrane +

inside and outside

 Overshoots exceeds the isopotential + 35 mV Spike potential: The sharp upward and downward curve of action potential

 Repolarization: The potential returns K+ channels open (slower than Na+ channels) K+ exits

K+

 After-hyperpolarization: Under the level of polarization

 Refractory periods: Unresponsive period to adequate stimulus Absolute: firing level 1/3 repolarization Relative: 1/3 repolarization the beginning of after-

depolarization (neurons can be stimulated by a largerthan-normal stimulus)

 All or none law Saltatory conduction: The

jump of depolarization from one Ranvier node to the next Ranvier node many voltage-gated channels present in Ranvier nodes ionic currents flow through cytosol & ECF energy-efficient mode of conduction (less ATP for Na+/K+ pumps)

Factors affecting the speed of conduction: 1. The amount of myelination 2. The diameter of axon (the larger the diameter of an axon,

the faster the propagation of impulses larger surface

areas) 3. Temperature (slower conduction at lower temperature) Encoding stimulus intensity Frequency of impulses Number of sensory neurons activated

The Types of Nerve Fibers in Mammalian Nerves

Type Function Diameter Conduction Duration Absolute (m/sec) (msec) refractory (m) period
12 -20 5 - 12 70 - 120 30 - 70 0,4 0,5 0,4 - 1

A A

Proprioceptive, somatic motor Touch, pressure

A
A

Motor in muscle spindle

Pain, cold, touch

3-6
2-5

15 - 30
12 - 30

Type Function

Diameter Conduction Duration Absolut (m/sec) (msec) refractory (m) period

<3 3 - 15 1,2 1,2

Autonomic preganglion

Pain, 0,4 1,2 temperature, some mechanoreceptive , reflex responds 0,3 1,3

0,5 - 2

Simpa Pre-ganglion thetic

0,7 2,3

PS: A & B fibers myelinated; C fiber unmyelinated

 Synapses Axodendritic

Axosomatic
Axoaxonic Synapses

Electrical synapses gap junctions connexons

Chemical synapses neurotransmitters

Once the action potential reaches the axon terminal:

Voltage-gated Ca+2 channels open Ca+2 enters the cells exocytosis of synaptic vesicles neurotransmitters

released

 Synaptic delay: The interval for the transmitters to traverse

the synaptic cleft neurotransmitters receptors in ligandgated channels One-way conduction: transmitters are only in pre-synaptic cells Orthodromic conduction Antidromic conduction Post-synaptic potentials graded local potentials

spread around local cells membrane

 Excitatory Post-Synaptic Potentials (EPSP)

Partial depolarization which decreases membrane potential/

increases neuronal excitability

Cation channels open (Na+, K+, Ca+2)

Na+ enters cells > Ca+2 inflow or K+ outflow

Local depolarization action potential, but facilitating action potential

 Inhibitory Post-Synaptic Potentials (IPSP)

The increase of negative potential inside cells -90 mV

(hyperpolarizing post-synaptic potential) Opening of Cl- or K+ channels (Cl- enter to the cells and K+ exit from the cells), or Na+ and Ca+2 channels are closed

Cells body/ soma integrates EPSP and IPSP

An example of excitatory and inhibitory system skeletal muscles motor neuron

Examples of inhibitory system organization:

Negative feedback (Renshaw cell), spinal motor neuron Cerebral cortex, limbic system, cerebellum

Spatial summation

Temporal summation

Repeated stimulation of one pre-synaptic neuron on a Simultaneous stimulation of many pre-synaptic post-synaptic neuron

neurons on one postsynaptic neurons

Characteristics
Origin Channels Conduction Amplitude

Graded Potential Action Potential

Dendrites/ Soma Trigger zone of an axon Ligand-gated/ Voltage-gated (Na+ mechanically gated and K+) Local, not Propagated propagated

Stimulus intensity All-or-none (100

(1 mV 50 mV) mV)

Duration
Polarity Refractory period

Longer (msec min) Hyperpolarizing/ Depolarizing Not present

Shorter (0.5 2 msec) Depolarizing Polarizing Present

Ion Channels
1. Leakage channels K+ leakage channels > Na+ leakage channels 2. Voltage-gated channels open/ close in response to a change in membrane potential Na+, K+, Ca+ 3. Ligand-gated channels open/ close in response to a specific chemical stimulus (neurotransmitter, hormones, ions) directly or indirectly (second messenger system) Na+, Ca+ inward, K+ outward 4. Mechanically gated channel open/ close in response to

mechanical stimulation (vibration, pressure, stretching) auditory receptors, stretch receptors of internal organs, touch receptors of skin

References 1. Barrett KE, Barman SM, Boitano S, Brooks HL (2010). Ganongs Review of Medical Physiology. 23rd ed. Chapter 4, Pages: 79-89; Chapter 6, Pages: 115-123. 2. Carola R, Harley JP, Noback CR (1990). Human Anatomy & Physiology. Chapter 11, Pages: 309-327 3. Guyton AC, Hall JE (2006). Textbook of Medical Physiology, 11th ed. Chapter 5, Pages: 57-71; Chapter 45, Pages: 555-571 4. Tortora GJ, Derrickson BD (2009). Principles of Anatomy and Physiology. 12th ed. Chapter 12, Pages: 417-447