NERVE TISSUE Part 2 NERVE TISSUE Part 2 Instructor Terry Wiseth ANATOMY & PHYSIOLOGY ANATOMY &...

NERVE TISSUEPart 2

NERVE TISSUEPart 2

Instructor Terry Instructor Terry WisethWiseth

ANATOMY & PHYSIOLOGYANATOMY & PHYSIOLOGY

2

MEMBRANE POTENTIAL AND MEMBRANE POTENTIAL AND NERVE IMPULSE NERVE IMPULSE TRANSMISSIONTRANSMISSION

Resting neurons maintain a difference in electrical charge across their cell membranes

+ + + + + + + + + + + + + + + + +

+++++++++++++++++- - - - - - - - - - - - - - - - -

-----------------

3


The inside of the resting neuron is negatively charged, the outside is positively charged

+ + + + + + + + + + + + + + + + +

+++++++++++++++++- - - - - - - - - - - - - - - - -

-----------------

4


When a neuron is stimulated this polarity is reversed, these reversals are called action potentials

+ + + + + - - - + + + + + + + + +

+++++++++---+++++- - - - - + + + - - - - - - - - -

---------+++-----

5

ACTION ACTION POTENTIALPOTENTIAL

Nerve impulses are conducted along the neuron by a wave of membrane polarity reversals (action potentials)

6

ACTION ACTION POTENTIALPOTENTIAL

Chemical messengers (neurotransmitters) carry nervous impulses from one neuron to another across the synapse

7

THE NEURON MEMBRANE AT THE NEURON MEMBRANE AT RESTREST

Neuron maintains a resting membrane potential of about -70 millivolts across the cell membrane

Sodium (NaNa++) and potassium (KK++) are the main ions involved

8

THE NEURON MEMBRANE AT THE NEURON MEMBRANE AT RESTREST

NaNa++ and KK++ cannot pass through the lipid bilayer membraneMove through the membrane by

using membrane proteins (pumps)

9

MEMBRANE PROTEINSMEMBRANE PROTEINS

Membrane proteins do several things: Some "leak" ions all the timeSome "leak" ions only when the cell

has been stimulated (ion "gates")Some "pump" ions by active

transport

10

NaNa++ / K / K++ PUMP PUMP

Membrane proteins actively transport Sodium out of the cellPotassium into the cell

Click Here to See Next Image




11

NaNa++ / K / K++ PUMP PUMP

Three Na+ are pumped out for every two K+ pumped in

Result is the cell has more Na+ on the outside and more K+ on the inside

Na+ Na+Na+

Na+ Na+ Na+ Na+

Na+

Na+

Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+

K+ K+ K+ K+ K+K+

K+ K+ K+ K+ K+ K+ K+ K+ K+ K+

K+K+ 18+

18+17+

19+

Cell MembraneNa+ / K+ Pump

12

Na+ / K+ PUMPNa+ / K+ PUMP

The pumping of Na+ out makes the outside moremore positive and the inside of the cell moremore negative

13

STIMULATED NEURONSTIMULATED NEURON

Nerve cells are unique in their ability to carry a signal using membrane potential changes

14


Stimulation of a neuron opens some of the membrane proteins(a.k.a. Na+ gates)Allows Na+ to pass freely into

the cells

15


Free flow of Na+ into the cell causes a reversal of membrane polarity

Polarity reversal is called the action potential

16

ACTION POTENTIALACTION POTENTIAL

Reversal of polarity (action potential) moves along the cell like a wave

The membrane restores the resting potential very quicklyIn less than 7 milliseconds the cell

can be stimulated again

17

ALL-OR-NONE ALL-OR-NONE RESPONSERESPONSE

Once a threshold limit is reached any stronger stimulus will not increase the cell's response

A stimulus below the threshold also will not stimulate the neuron

18

SYNAPSESYNAPSE

Neurons communicate across the synapse by using chemical messengers called neurotransmitters

19

SYNAPSESYNAPSE

Neurotransmitters may act to inhibit neurons or to excite neurons

20

SYNAPSESYNAPSE

Attachment of the neurotransmitters to presynaptic membrane receptors causes ion channels to open Generate an action potential

21

MEMBRANE POTENTIALMEMBRANE POTENTIAL

Plasma membrane exhibits membrane potentialResting potential

Electrical voltage difference across the membrane

22


With stimulation resting potential can produce responses called action potentials

23


Resting potential is like voltage stored in a battery

Electric current produced by flow of electrons from negative to positive current

24


Action potentials occur because plasma membrane contains ion channels that open or close in response to stimuli

25

ION CHANNELSION CHANNELS

Non-gated channelsAlways open

Gated channels Open or close in response to

stimuli

26

ION CHANNELSION CHANNELS

Plasma membrane has many more K+ non-gated channels than Na+ non-gated channelsThus membrane permeability

to K+ is higher

27

GATED CHANNELSGATED CHANNELS

Gated channels are stimulated by:VoltageChemicalsMechanical pressureLight

28

RESTING MEMBRANE RESTING MEMBRANE POTENTIALPOTENTIAL

Occurs because of the build-up of negative charges in the cytosol (intracellular fluid)

Equal build-up of positive charges in the extracellular fluid just outside the membrane

29


Separation of charges represents potential energy measured in millivolts

Large +/- difference = large potential

30


Potential exists only at membrane surfaces

Resting membrane potential in the neurons is -70mV

Cells with membrane potential are polarized

31


Factors contributing to resting membrane potential1) Unequal distribution of ions2) Relative permeability of the

cell membrane

32


1)1) Unequal distribution of ions across the plasma membraneExtracellular fluid

Rich in Na+ and Cl-

Intracellular fluidK+ and PO4

-, amino acids -

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

33


2) Relative permeability of the cell membrane to Na+ and K+

Resting neuron permeability 50 to 100 times greater to K+ than to Na+

34

MEMBRANE MEMBRANE PERMEABILITYPERMEABILITY

Cell membrane has a low permeability for Na+ from outside of cell and Pr- inside cells

Membrane has high permeability to K+ to move out of cell

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

Click to see theanimation again

35


Cell membrane has a low permeability for Na+ from outside of cell and Pr- inside cells

Membrane has high permeability to K+ to move out of cell

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

Click to see theanimation again

36


Tendency for K+ to move from inside the cell to outside down the concentration gradient

As K+ move out Na+ move down its concentration gradient into the cell

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

37


This has the effect of balancing electrical effect of K+ outflow

Na+

K+ K+ K+ K+ K+

Na+ Na+ Na+ Na+Na+

K+

Na+

K+

Na+

K+

38


But Na+ inward flow is too slow to keep up with K+ outflow

Net effect of K+ outflow is that the inner cell membrane surface becomes more negative

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

39

NaNa++ /K /K++ PUMPS PUMPS

Both electrical and concentration gradients promote Na+ inflow

Na+ Cl-

K+PO4

- AA-

AA-AA-

AA- K+

K+K+

K+

K+

PO4-

PO4-

PO4-

PO4-

Na+ Na+

Na+Na+

Na+Cl- Cl-Cl-

Cl-

Cl-Cl-

40


Small inward Na+ leak is taken care of by Na+ / K+ pumps

Maintain resting membrane potential by pumping out Na+ as fast as it leaks in

NaNa++ / K / K++ PUMPSPUMPS K+

Cell exterior

Cell interior

Na+

Na+ K+

Pump

Axon interior

Na+

150 mMK+

5 mM

K+

150 mM

Na+

15 mM++

+ ++ +

++

+ ++ +

++

+ ++ +

++

+ ++ +

++

+ ++

++

++ +

+ ++

++ +

+ ++

++ +

+ ++

++ +

+ ++

++ +

+

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

-70mV (across membrane

Axon exterior

Na+ / K+ pumps bring in K+ K+ redistributes immediately

because it is permeable to the membrane

Click toClick toView ImageView Image

42


Thus the critical job of the Na+ / K+ pumps is to expel Na+

Total effect is -70 mV resting membrane potential

43

ACTION POTENTIALSACTION POTENTIALS

"impulse"Occurs when depolarization is

large enough at a trigger zone

44

ACTION POTENTIALSACTION POTENTIALSDepolarization

Membrane becomes less negative (more positive) than the resting level

45

IMPULSEIMPULSE

Sequence of rapidly occurring events that decrease and reverse the membrane potential (depolarization)and then restore it to the resting state (repolarization)

46

Impulse Impulse SummarySummary

1)1) Resting Potential2)2) NaNa++ gates open 3)3) NaNa++ enters axon4)4) NaNa++ gates close 5)5) KK++ gates open6)6) KK++ flows out of axon7)7) KK++ gates close

47

IMPULSEIMPULSE

Two types of voltage gated ion channels open and close

Na+

K+

Na+

Na+

Na+

Na+

Na+

Na+Na+Na+ Na+

Na+

Na+Na+Na+

Na+Na+

Na+

Na+Na+

Na+

Na+

K+K+

K+

K+

K+

K+

K+

K+K+

K+

K+

K+

K+

K+

K+ K+ K+

K+

K+

K+

K+K+

30

0

-70

mV

Click to Click to View View

AnimationAnimation

Click to Click to View View

AnimationAnimation

48

IMPULSEIMPULSE

1)1) First channels to open allow Na+ to rush into the cell causing depolarization

49

IMPULSEIMPULSE

2)2) Second channels open allowing K+ to flow out producing repolarizationLasts about 1 millisecond

(1/1000 sec)

50

DEPOLARIZATIONDEPOLARIZATION

Stimulus causes inflow of Na+ bringing membrane potential from -70 mV to +30 mV

51

DEPOLARIZATIONDEPOLARIZATION

Voltage gated Na+ channels open just long enough for about 20,000 Na+ ions to flow in

Na+ pumps bail the Na+ back out to the extracellular fluid

52

REPOLARIZATIONREPOLARIZATION

Voltage gated K+ channels opened by depolarization Results in out flow of K+ ionsCausing recovery of resting

membrane potential

53

REPOLARIZATIONREPOLARIZATION

Na+ ion channels closeK+ channels openMembrane potential changes

from +30 mV to 0 mV to -70 mV

54

REFRACTORY PERIODREFRACTORY PERIODTime where excitable cell cannot

generate another action potential

Click the image to slow the impulse down

55

PROPAGATION OF PROPAGATION OF NERVE IMPULSESNERVE IMPULSES

Nerve impulses occur in two different ways1) Continuous conduction2) Saltatory conduction

56

CONTINUOUS CONTINUOUS CONDUCTIONCONDUCTION

Unmyelinated axonsMuscle cells

57


Dominoes (self-propagation)Normally moves only one

direction from where it arises

Click toView Animation

58


Dominoes (self-propagation)Setting the dominoes back up

simulates repolarization


59

LOCAL ANESTHETICSLOCAL ANESTHETICSNovocaine / lidocaine used to block pain

Block opening of voltage gated Na+ channels

Na+

K+

Na+

Na+

Na+

Na+Na+

Na+Na+Na+ Na+

Na+

Na+Na+Na+

Na+Na+

Na+

Na+Na+

Na+

Na+

K+K+

K+

K+

K+

K+

K+

K+K+

K+

K+

K+

K+

K+

K+ K+ K+

K+

K+

K+

K+K+


60

SALTATORY SALTATORY CONDUCTIONCONDUCTION

Myelinated axonsMyelin sheath acts as an insulatorBlocks ionic currents across the

membrane

61


Nodes of RanvierInterrupt

myelin sheathHigh density of

voltage-gated Na+ channels

Membrane depolarization can occur

62


Currents carried by Na+ and K+ can flow across the plasma membrane

63


Currents carried by ions through extracellular fluid around myelin sheath

Current flows across membrane only at nodes

64


Impulse appears to leap from node to node

65


Current travels faster than in continuous conduction in fibers of equal diameter

66

SPEED OF IMPULSESPEED OF IMPULSE

1)1) Diameter of fibers2)2) Presence or absence of myelin

sheath3)3) Temperature

ex. Pain reduced by localized cooling of nerve

67

FIBER DIAMETERFIBER DIAMETER

Largest diameter called A fibersAll myelinatedSpeed 12-130 m/sec (27-280

mph)Touch, pressure, propriception,

heat, cold, skeletal musclemotor nerves

Exist where quickreactions are critical

68


B fibers Myelinated15 m/sec (32

mph)Sensory

viscera nerves

69


C fibers (smallest) Unmyelinated2m/sec (1-4 mph)Pain from viscera

70

IMPULSE SPEEDIMPULSE SPEED

Large diameter axons can transmit up to 2500 impulses/sec

Small diameter axons can transmit only 250 impulses/sec

Normal rate is10-1000 impulses/sec

71

NEUROTRANSMITTERSNEUROTRANSMITTERS

Neurotransmitters are released during a synapseNeurotransmitters are chemicals

which are able to stimulate an action potential on another neuron

72


Neurotransmitters cause either 1) Excitatory potentials2) Inhibitory potentials

73

REMOVAL OF REMOVAL OF NEUROTRANSMITTERNEUROTRANSMITTER

Neurotransmitters must be removed from the synaptic cleft or there would be a constant stimulus for an action potential1)1) Diffusion2)2) Enzymatic degradation

ex. acetylcholinesterase3)3) Cellular reuptake

74

DIFFUSIONDIFFUSION

The neurotransmitter drifts away, out of the synaptic cleft where it can no longer act on a receptor

75

ENZYMATIC ENZYMATIC DEGRADATIONDEGRADATION

Neurotransmitters are broken down by enzymes into non-initiating by products

76


Nerve gas and some insecticides work by interfering with acetylcoholinesterase and thus a build up of the neurotransmitter aceylcholine in the synaptic cleft

Normal ACh

action

Interference of Nerve gas

on AChE

77


Causes a continuous initiation of the nerve impulse with no relaxation

Atropine is an antidote for nerve gas

78

CELLULAR REUPTAKECELLULAR REUPTAKE

Active transport of neurotransmitter back into the neuron that released them (recycling)

79

CELLULAR REUPTAKECELLULAR REUPTAKE

Cocaine produces intense pleasurable euphoria because it blocks transporters for the reuptake of dopamine

80

REMOVAL OF REMOVAL OF NEUROTRANSMITTERNEUROTRANSMITTER

Allows dopamine to linger in synthetic cleft

Excessively stimulating certain brain regions

81


Excitatory and inhibitory neurotransmitters found in both PNS and CNS

82

NEUROTRANSMITTERSNEUROTRANSMITTERSSame

neurotransmitter may be inhibitory in one location but excitatory in anotherEx: ACh

Type of receptors determines which response occurs

83

ACETYLCHOLINEACETYLCHOLINEExcitatory at neuromuscular junctionActs to open chemically gated ion

channels

84

ACETYLCHOLINEACETYLCHOLINE

Inhibitory in parasympathetic fibers of Vagus nerve (cranial nerve X)Innervates the heartSlows the heart rate down

85

KNOWN KNOWN NEUROTRANSMITTERSNEUROTRANSMITTERS

60 known neurotransmittersParkinson's Disease, Alzheimer's

Disease, depression, anxiety and schizophrenia are caused by neurotransmitter problems

86


Neurotransmitters are grouped by chemical similarities1) Small molecule

neurotransmittersubstances

2) Amino acids3) Neuropeptides4) Soluble gases


Small Molecule Neurotransmitter SubstancesAcetylcholine (ACh) Dopamine (DA) Norepinephrine (NE)

Serotonin (5-HT) Histamine Epinephrine

Amino AcidsGamma-aminobutyric

acid (GABA)Aspartate Glycine Glutamate

Soluble Gases

Nitric Oxide (NO) Carbon Monoxide

NeuropeptidesBradykinin Endorphin Bombesin Calcitonin

Cholecystokinin Enkephalin Dynorphin Insulin

Gastrin Substance P Neurotensin Glucagon

Secretin Somatostatin Motilin Vasopressin (ADH)

Oxytocin Prolactin Thyrotropin Angiotensin II

Sleep peptides Galanin Neuropeptide Y Vasoactive intestinal peptide

Gonadotropnin-releasing hormone

Growth hormone-releasing hormone

Luteinizing hormone Thyrotropin-releasing hormone

88


Released at neuromuscular junction

89


Released by axons of limbic system in brainDestruction of these neurons is a

hallmark of Alzheimer's Disease

90

AMINO ACIDSAMINO ACIDS

Glutamate and aspartate are excitatory in the brain

GABA and glycine are inhibitory

91

AMINO ACIDSAMINO ACIDS

GABA found primarily in the brainAntianxiety drugs (valium)

enhance the action of GABAGlycine found primarily in the

spinal cord

92

STRYCHNINE STRYCHNINE POISONINGPOISONING

Normally neurons release inhibitory glycine in spinal cord to motor neurons to prevent excessive muscular contraction

93

STRYCHNINE STRYCHNINE POISONINGPOISONING

Strychnine binds and blocks glycine receptors

Result is massive tetanic contractions

94

NOREPINEPHRINE (NE) NOREPINEPHRINE (NE) & EPINEPHRINE& EPINEPHRINE

May act as inhibitory or excitatoryImplicated in maintaining arousal,

dreaming and mood regulation

95

DOPAMINE (DA)DOPAMINE (DA)

Involved in emotional responsesRegulate gross automatic

movements of skeletal muscles

96

DOPAMINE (DA)DOPAMINE (DA)Degeneration of neurons producing

dopamine causes Parkinson's Disease

97

SEROTONIN (5-HT)SEROTONIN (5-HT)

Induce sleep, sensory perception, temperature regulation and control of mood

98

SEROTONIN (5-HT)SEROTONIN (5-HT)

Anti-depressant (Prozac) is a serotonin inhibitor of serotonin reuptakeThus more serotonin available in

synaptic cleftAllowing signals to pass from

neuron to neuron more easily

99

NEUROPEPTIDESNEUROPEPTIDES

May also act as hormonesLargest class of neurotransmitters

NeuropeptidesBradykinin Endorphin Bombesin Calcitonin

Cholecystokinin Enkephalin Dynorphin Insulin

Gastrin Substance P Neurotensin Glucagon

Secretin Somatostatin Motilin Vasopressin (ADH)

Oxytocin Prolactin Thyrotropin Angiotensin II

Sleep peptides Galanin Neuropeptide Y Vasoactive intestinal peptide

Gonadotropnin-releasing hormone

Growth hormone-releasing hormone

Luteinizing hormone Thyrotropin-releasing hormone

100

NEUROPEPTIDESNEUROPEPTIDES

Angiotensin IIStimulates thirst

OxytocinImproves memory

101

NEUROPEPTIDESNEUROPEPTIDESAntidiuretic hormone (ADH)

Also called vasopressinRegulates water reabsorption

Enkaphalins and endorphinsAnalgesic effects

102

ENKAPHALLINS AND ENKAPHALLINS AND ENDORPHINSENDORPHINS

Linked to improved memory, learning, feelings of pleasure and euphoria200 X stronger than morphine

103

ENKAPHALLINS AND ENKAPHALLINS AND ENDORPHINSENDORPHINS

Acupuncture may increase release of enkaphalins and endorphins (opioids)

104

GASESGASES

Nitric oxide (NO)Released by endothelial cells

lining blood vesselsCauses relaxation

and vasodilationEffect is tolower BP

105

NITRIC OXIDENITRIC OXIDE

Phagocytic cells produce NO to kill microbes and tumor cells

In large quantities NO is toxic

106

ALTERATION OF ALTERATION OF IMPULSES AND IMPULSES AND

SYNAPSESSYNAPSESAlkalosisAcidosisHypnoticsCaffeine

107

ALKALOSISALKALOSIS

Increase in the pH above 7.45Increases the excitability of neuronsImpulses arise inappropriatelyLight headedness, numbness,

tingling, nervousness, muscle spasms

108

ACIDOSISACIDOSIS

Decrease in pH below 7.35Progressive depression of neuron

activityProduces apathy and muscle

weakness

109

EXCESSIVE PRESSUREEXCESSIVE PRESSURECauses blockage of nerve impulseCan cause appendages to "go to sleep"

110

HYPNOTICS, HYPNOTICS, TRANQUILIZERS, TRANQUILIZERS,

ANESTHETICSANESTHETICSIncrease the threshold for excitation

111

CAFFEINE, CAFFEINE, BENZEDRINE, BENZEDRINE,

NICOTINENICOTINEReduce threshold for excitation

112

CHEMICAL SYNAPSE CHEMICAL SYNAPSE MODIFICATIONMODIFICATION

Clostridium botulinum bacteria in some canned foods produce a toxin

Small amounts are very poisonous

113


Toxin inhibits the release of ACh if ingestedWeakens muscle contractions

114


Basis for Botox treatments

115


Strabismus, uncontrolled winking, stuttering are uncontrollable muscle contraction

Can be helped by injections of botulinum toxin

116

MYASTHENEA GRAVISMYASTHENEA GRAVIS

Weakened muscle condition brought on by antibodies blocking acetylcholine receptors

117

MYASTHENEA GRAVISMYASTHENEA GRAVIS

Neostigmine and phystigmineAnticholinesterase agents that

inactivate acetylcholinesteraseResults in slow removal of

acetylcholineUsed to treat myasthenia gravis

118

DIISOPROPYL DIISOPROPYL FLUOROPHOSPHATEFLUOROPHOSPHATE

Powerful nerve gasAnticholinesterase agent active

in many insecticides

119

CURAECURAE

Plant derivativeSouth American Indians poisoned

arrows and darts

120

CURAECURAE

Blocks acetylcholine receptors causing muscular paralysis

May be used during surgery to relax muscles

Neostigmine is antidote for curare

EndEndNerve TissueNerve Tissue

Part 2Part 2

NERVE TISSUE Part 2 NERVE TISSUE Part 2 Instructor Terry Wiseth ANATOMY & PHYSIOLOGY ANATOMY &...

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