Neurons

1. Neurons • A nerve cell capable of generating and transmitting electrical signals • Vary in structure and properties • Use the same basic mechanisms to send signals • Generate action potentials or passive potential • Communicate with other neurons or cells via synaptic connections (electrical or chemical)

2. Neurons

3. Structural Diversity of Neurons

4. Neuron Classification Based on Structure

5. Neuron Classification Based on Function

6. Neural Zones • Four functional zones • Signal reception: dendrites and the cell body (soma) - Incoming signal is received and converted to a change in membrane potential • Signal integration: axon hillock - Strong signal  action potential (AP) • Signal conduction: axon; some wrapped in myelin sheath - AP travels down axon • Signal transmission: axon terminals - Neurotransmitter is released

7. Neural Zones, Cont.

8. Electrical Signals in Neurons • Neurons have a resting membrane potential (like all cells) • Neurons are excitable; can rapidly change their membrane potential • Changes in membrane potential act as electrical signals

9. Measuring the voltage • Use microelectrodes to measure the voltage between outside and inside • Conducting fluid such as KCL is used • Reference electrode is placed in the bathing medium • Potentiometer will measure the potential ie • resting potential

10. Membrane Potential • Three factors contribute to the membrane potential • The distribution of ions across the plasma membrane • The relative permeability of the membrane to these ions • The charges of the ions ►Nernst equation can be used to measure the potential of a cell ie the voltage difference between the inside and the outside of the cell.

11. Membrane Potential EK+ = (1.9872*295)/(1*23062) ln (4/139) = - 88 mV at 22oC ENa+ = (1.9872*295)/(1*23062) ln (145/12) = 62 mV at 22oC ECl- = (1.9872*295)/(-1*23062) ln (116/4) = - 84 mV at 22oC

12. Resting potential Origin of the resting potential in a typical vertebrate neuron. • A- - negatively charged proteins • Resting neuron: 10 times more open K+ channels than Na+ or Cl- channels • Outside of cell is more positive relative to the inside of the cell • K+ isdominant because its permeability is greatest (PK). This is due to leak channels • So the resting potential is closest to the Nernst potential for K+ • Also have leakage of Na+ (PNa) and Cl- (PCl)

13. Resting potential Actual measurements of membrane potential • Measured in giant axon of squid • Found resting potential of -65 to -70 mV • Increased external K+ to determine new membrane potential • Found a slope of – 58 mV ► means that for every ten fold increase in external K+ the potential will increase by 58 mV at room temperature • So other ions are influencing the resting potential!! • Permeability of Na+ and Cl- ions and the presence of proteins. • Use Goldman equation to calculate the resting potential

14. Resting potential

15. Membrane Potential • Nernst equation predicts membrane potential for a single ion • Goldman equation for the membrane potential (Em): predicts the membrane potential using multiple ions Chloride ion has a charge opposite to the two cations, a correction is needed to prevent the cations and anion from canceling each other. Thus, the statement of relative chloride ion concentrations is inverted— inside over outside In the giant squid: PK+ : PNa+ : PCl- = 1 : 0.04 : 0.45

16. Membrane Potential • Effects of changing the ion permeability The resting membrane potential is -53 mV; ENa, EK, and ECl are the potentials calculated from the Nernst equation if the membrane contains only open channels for Na+ or K+ or Cl-, respectively.

17. Electrical signals • Changes in Channel permeability create Electrical signals! • Mechanically gated ion channels • Sensory neurons. Open in response to pressure or stretch • Chemically gated ion channels • Respond to ligands • Voltage gated Na+ channels • Respond to changes in membrane potential • Voltage gated K+ channels or CA2+ channels

18. Graded Potential vs. Action Potential Two types of electrical signals

19. Action potentials Active conduction • Passive conduction of signal is limited by properties of the nerve and signal is reduced over distance • Active conduction ie action potentials (AP) • - Signal travels along nerve with no loss of amplitude

20. Action Potentials (AP) • Occurs only when the membrane potential at the axon hillock reaches threshold • Three phases • Depolarization • Repolarization • Hyperpolarization • Absolute refractory period – incapable of generating a new AP • Relative refractory period – more difficult to generate a new AP

21. Voltage-Gated Channels • Change shape due to changes in membrane potential • Positive feedback, e.g., influx of Na+  local depolarization   number of open Na+ channels • Na+ channels open first (depolarization) • K+ channels open more sloooooowly (repolarization) • Na+ channels close • K+ channels close slooooowly (relative refractory period)

22. Channels of an Action potentials Voltage gated Na+ channels: 3 states: closed, open, inactive Closed to open: • Depolarization is necessary to open the channel • Acts to activate itself in a regenerative cycle • More Na+ influx depolarizes the membrane which opens more channels which depolarizes the membrane more. • Open to Inactive: • Depolarization is also necessary to inactive the channel • Once the channel is open it will then also switch to the inactive state and can not be opened again • Inactive to closed: • The channel will not switch back to the closed state until the membrane has repolarized (i.e. gone back towards the original resting membrane potential • Once in the closed state it can then be reopened

23. Na+ Channels Have Two Gates • Activation gate – voltage dependent • Inactivation gate – time-dependent

24. Na+ Channels Have Two Gates

25. Channels of an Action potentials Voltage gated K+ channels (delayed rectifying K+ channel): 2 states: closed and open Closed to open: • Strong depolarization is necessary to open the channel • Hyperpolarizes the cell • Brings membrane back towards Nernst potential for K+ • Open to Closed: • Will close when the membrane becomes hyperpolarized • Works to shut itself down

26. Voltage-Gated Channels, step by step

27. Action Potentials Travel Loooong Distances • “All-or-none” – occurs or does not occur; identical without degradation • Self propagating - an AP triggers the next AP in adjacent areas of the axonal membrane • Electronic current spread in between ion channels • Cycle: Ion entry  electronic current spread  triggering AP

28. Components of an Action potentials

29. Components of an Action potentials • Threshold • Most neurons have a threshold at -50 mV (i.e. 10 to 15 mV depolarization) • Action potential is an all or none event. If a nerve is at rest the amplitude • on one action potential will be the same all along the nerve independent of the • stimulus strength • Threshold reflects the need to trigger the opening of the voltage-gated • sodium channel (need a depolarization of about 10 to 15 mV to open) • Rising phase • Sodium channels open • Na+ ions flow into cell • Depolarizes the cell • More and more sodium channels open = a regenerative response regenerative opening of sodium channels drives the membrane potential towards a peak of the Nernst equilibrium potential for Na+

30. Components of an Action potentials • Peak • During an action potential the membrane potential goes towards the • Nernst equilibrium potential for Na+ • In terms of Goldman-Katz equation now permeability to Na+ is dominant • (K+ and Cl- minor components) therefore membrane potential goes towards • ENa • Usually falls short of ENa, less driving force on Na+ and the channels begin • to inactivate rapidly after activation

31. Components of an Action potentials • Fall • Membrane potential falls back towards rest- Why doesn't the action potential stay around ENa?Two reasons: i) Na+ channels move into an inactive stateii) delayed K+ channels open • Inactivating Na+ channels- Na+ channels go to an inactivated state after 1-2 msec after first opening - inactivated = can NOT be reopened- Membrane potential now determined mostly by K+ (same as for resting potential) and membrane starts to repolarize • Delayed K+ channels open (delayed rectifier; voltage-gated like Na+ channel)- open after about 1-2 msec of threshold depolarization- now K+ flows out of the cell and speeds the repolarization process- cause the hyperpolarizationafter the action potential - open K+ channels make the K+ permeability higher than at rest - membrane more negative on inside - hyperpolarization of membrane causes K+ channels to close - Membrane settles back to rest

32. Components of an Action potentials • Repolarization • Voltage-gated Na+ channels and voltage-gated K+ channels now closed • Membrane goes back to the resting state- i.e. the leak channels are the only channels open and again set the membrane potential

33. Unidirectional Signals • Stimulus starts at the axon hillock and travels towards the axon terminal • Up-stream Na+ channels (just recently produced an AP) are in the absolute refractory period • The absolute refractory period prevents backward transmission and summation of APs • Relatively refractory period also contributes by requiring a very strong stimulus to cause an AP

34. Refractory period (RP) Absolute RP • Na+ channels are inactive and CAN NOT be opened no matter how much • the membrane is depolarized at this time • another action potential can not be generated Relative RP • Membrane repolarizes ---- • goes to more negative potentials • Triggers the Na+ channels to move • from an inactive state to a close state • Hyperpolarization by the opening of the • K+ channels • Once Na+ channel is in the closed state • it can be opened again with depolarization • during relative RP, more and more • Na+ channels available to be opened and • therefore increase the chances of firing • an action potential

35. Refractory period (RP)

36. Frequency of AP How does a nerve communicate the strength of a stimulus? • Information is given by the frequency of the AP along the nerve • Stimulus strength triggers different frequency of AP • For example: light touch – infrequent AP; • rough touch – more frequent AP • Refractory period limits the frequency of AP • During the relative RP an AP can be generated • but has to be at supra threshold because it has to • overcome the hyperpolarization • Will be at decreased amplitude because • fewer Na+ channels are available to open

37. Direction of AP Unidirectional conduction of an action potential due to transient inactivation of voltage-gated Na+ channels

38. Action Potentials Travel Loooong Distances • Triggered by the net graded potential at the axon hillock(trigger zone) • Do not degrade • Travel looong distances • All-or-none • Must reach threshold potential to fire

39. Action Potentials Travel Looong Distances

40. Action Potentials Travel Looong Distances

41. Signals in the Dendrites and Cell Body • Incoming signal, e.g., neurotransmitter • Membrane-bound receptors transduce the chemical signal to an electrical signal by changing the membrane potential (graded potential)

42. Graded Potentials • Vary in magnitude depending on the strength of the stimulus • e.g., more neurotransmitter  more ion channels will open

43. Graded Potentials • Ions move down an electrochemical gradient • Net movement stops when the equilibrium potential is reached • Can depolarize (Na+ and Ca2+ channels) or hyperpolarize (K+ and Cl- channels) the cell

44. Graded Potentials Travel Short Distances • Conduction with decrement –  strength with  distance from opened ion channel • Due to • Leakage of charged ions across the membrane • Electrical resistance of the cytoplasm • Electrical properties of the membrane • Electrotonic current spread – positive charge spreads through the cytoplasm causing depolarization of the membrane • Can be excitatory or inhibitory

45. Graded Potentials Travel Short Distances

46. Integration of Graded Signals • Many graded potentials can be generated simultaneously • Many receptor sites • Many kinds of receptors • Temporal summation – graded potentials that occur at slightly different times can influence the net change • Spatial summation – graded potentials from different sites can influence the net change

47. Spatial summation

48. Temporal summation

49. Integration of Graded Signals, Cont.

50. Back to Neuron structure