Electrical and concentration gradient driving forces for Sodium and Potassium
How does the membrane potential change if 1) permeability to sodium increases2) Permeability to potassium increases
Why is resting membrane potential closer to EK than ENa?
What would happen to membrane potential if suddenly PNa
became very great?
Size and Direction of Arrows show driving forces!
The G-H-K Equation!S 8
The Goldman Hodgkin Katz Equation
• If you know the concentrations of ALL permeable ions and their relative permeabilities, you can calculate the membrane potential using the GHK Equation.
S 9
At RMP, some Na+ leaks in, some K+ leaks out.
S 10
Which ion moving in which direction (into or out of cell) is responsible for depolarization and overshoot? Which ion moving in
which direction (into or out of cell) is responsible for repolarization and hyperpolarization?
Can the membrane potential go more negative than -90 mV?
Increase PK+
Increase PNa+
S 14
Increase PK+
How do ions get across the membrane? Ion channels!
Graded potentials are conducted decrementally for only a few millimeters, die out over distance and time, and are proportional to the size of the stimulus.
Leak ChannelsGated Channels….. Ligand-gated….. Mechanically-gated….. Voltage-gated
Electrogenic Sodium-Potassium ATP-ase maintains concentrations across membrane
2K+
3 Na+
S 15
Graded potentials are conducted no more than 2mm
Insect bites foot (stimulus).Sensory neuron produces graded potential in proportion to intensity of the stimulus.How is signal conducted to the brain?
S 17
Leak ChannelsGated Channels….. Ligand-gated….. Mechanically-gated….. Voltage-gated
Interneurons & Motoneurons
Sensory neuronTypes and locations of Ion Channels
Intracellular RecordingElectrode orStimulating Electrode
S 3
w/ LGCs and MGCs
w/ VGCs
w/ LGCs
How is the intensity of a stimulus encoded by action potential if all action potentials have the same size (amplitude)?
What happens when the membrane is depolarized by more than about 15 mV?
Action potentials are all or nothing.Analogy of shutter release pressure on a camera, either trips shutter or not.
S 4 Expanded on next slide
S 5
Relevance of the GHK equation
Changes in membranepermeability produce changes inmembrane potential via the openingand closing of ion channels!
To reset from inactivated state to closed state, membrane must repolarize.
Compare and contrast voltage-gated Na and K channels based on time to open and duration of open time.
Open at -55 mV
Membrane must repolarize to “reset” Na+ Channels to be capable of opening again.
S 6
Voltage-gated Na+ channel
scienceblogs.com/.../upload/2006/03/channel.jpg
Tetrodotoxin from ovary ofPuffer fish, used in Japanese sushi (fugu)
S 7
What types of ion-channels are labeled in this neuron in red?
S 8
TTX with red fluorescent marker
Relative permeabilitiesDuration of APRefractory periods
absolute RPrelative RP
Properties of V-gated Na+ and K+ channels account for the shape of the action potential and the refractory periods.
Why does the peak of the action potential not reach ENa?
RisingPhase
FallingPhase
S 9
S 10
Natural ways to Initate an Action Potential
Graded depolarization in cell body reach threshold at axon hillock
Graded depolarization in in receptive membranes of sensory neurons reach threshold for AP at trigger zone. i.e. nociceptors and stretch receptors.
Unstable membrane potential cycles: pacemaker potentials in pacemaker cells of heart, smooth muscles of gut, and medullary neurons for respiratory rhythm.
S 11
Who Cares?
Novacaine, lydocaine, xylocaine, All block voltage-gated Na+ channelsPrevent action potentials, so stimulus does not result in an action potential in sensory neurons which would convey that information to the brain where person would be conscious of the stimulus!
S 12
Axon Hillock
Axon
Questions About Action Potential Conduction:How does an action potential move along the axon? Why doesn’t the amplitude get smaller with distance?Why is the conduction of an action potential unidirectional? What is the absolute refractory period and what is going on with voltage gated sodium channels that accounts for the absolute refractory period?What is the relative refractory period and what is going on with voltage gated sodium channels that accounts for the relative refractory period?
S 13
In unmyelinated axons, action potential must be generated at each point along the membrane, a relatively slow process that involves influx of Na+ which sets up positive feedback cycle.
In myelinated axons, action potential must be generated only at the nodes of Ranvier, which allows AP to be conducted much faster and with fewer ions moving, and thus less energetically expensive.
S 14
Axon Hillock ofinterneuron or efferent neuron
Axon
The Questions:How does an action potential move along the axon? Why doesn’t the amplitude get smaller with distance?Why is the conduction of an action potential unidirectional?
S 1
Trigger Zone of Sensory Neuron
Figure 6.23
AP CV (up to 100 m/s)Location of channelsEnergy RequirementsAxon diameterClustering of V-gated channels at Nodes of Ranvier
Reminder: influx of Na+ is very quickly followed by efflux of K+ (not shown above)
Saltatory ConductionS 3 What’s at theend of an axon?
Figure 6.24Section C: Synapses and Synaptic Transmission
S 4
Anatomy of an Electrical Synapse (aka Gap Junction)
Comparison to Chemical Synapses•Directionality •Response time•Sign inversion?
Uncommon in human CNS.Common in cardiac muscleand some smooth muscle.
S 8
S 5
Anatomy of a Chemical Synapse
Presynaptic cell
Postsynaptic cell
S 6
Figure 6.27
Vesicle release proportional to Ca++ influx (High f AP leads to residual Ca++ in terminal)
Fates of neurotransmitters:1)Bind to receptor on Post-synaptic cell2)Diffusion away from synapse3)Enzymatic degradation e.g. Acetylcholinesterase (AChE) and Monoamine Oxidase (MAO)4)Uptake by astrocytes5)Reuptake into presynaptic terminal (e.g. SSR)
S 7Most neurotransmitters are synthesized in the axon terminal.Exceptions: Peptide NTs originate in cell body, move in vesicles by fast orthograde axonal transport to axon terminal.
Tetanus toxin & Botulinum toxin disrupt SNARE function.
Figure 6.33Presynaptic FacilitationPresynaptic Inhibition
Who Cares?
Mechanism: vary Ca++ entry in presynaptic terminal B.
Size of PSP is Variable!
S 8
Figure 6.25UnidirectionalRelease, diffusion, binding,Post-synaptic Receptor Types: Inotropic or Metabotropic
Classification:Excitatory (closer to threshold for AP)OrInhibitory (stabilizes or hyperpolarizes)
S 1
Inotropic receptor Metabotropic receptor
Types of Acetylcholine Receptors so named for agonist:Nicotinic AChR and Muscarinic AChR
Types of Ligand-Gated ReceptorsS 2
Agonist = Nicotine Agonist = Muscarine
Antagonist = Curare Antagonist = Atropine
= ACH = Acetylcholine
Priority by proximityTo axon hillock!
S 3
Figure 6.28
EPSPs :which ion moving in which direction?Duration of PSP vs APSynaptic delay
Some ion Channels that allow flux of Na+ and K+ simultaneouslye.g. nicotinic Acetylcholine Receptor (nAChR)
S 4
Figure 6.29
IPSPs :which ion moving in which direction?
Some IPSPs result in no change in membrane potential by opening Chloride channels that stabilize membrane potential at resting value (Nernst Potential for Cl- = -70mV) or in cells that actively transport Cl- out.
EK+
S 5
Figure 6.31
Summation and Synaptic Integration
Different times Different locations
Challenge question: Suppose each IPSP hyperpolarizes by 5 mV and each EPSP depolarizes by 5 mV.If 4 inhibitory synapses are active at the same time, how many excitatory synapses must be active simultaneously to exceed threshold (-55 mV) if the resting membrane potential is -70mV?
S 6
Synapses named for NT used: -ergic
Examples:CholinergicAdrenergicSerotonergicGABAergicPeptidergic
S 7
Pharmacological agents intended to act in brain must be able to cross blood-brain barrier.
Who Cares?
Parkinsons Disease
Treatments for Parkinsonism: a) tablets of L-Dopa (which crosses the BBB) unlike Dopamine (which would have widespread effects)b) neuronal transplants (self, fetal, stem cell, pig), c) electrical stimulation NIH Stem Cell Information
S 11
Nerves & Ganglia
Tracts, pathways, commissures
Nuclei
Control of digestive functions in quadraplegics via enteric nervous system.
12 pairs of cranial nerves31 pairs of spinal nerves
SkeletalMuscle
Vision, taste,smell, hearing,equilibrium
Touch, pain,temperature,proprioception
Smooth muscleCardiac muscleGlands
S 3
Vessel stretch,O2, CO2, etc.
Figure 6.38S 4
Figure 6.39Components of gray matter
Amygdala &Hippocampus
S 5
How do we know the functions of various brain regions?
a) Correlations of deficits of stroke victims with brain regions affected.b) Selective ablations.c) Selective electrical and chemical microstimulation
i) Dr. Hettes’s experiments on ratsii) Neurologist Wilder Penfield & Epilepsy
Analogy: experiments to discover the function of a battery in a car.
S 6
S 7
Homunculus = representation of body parts
S 8
Dorsal roots = sensory (afferent)Ventral roots = motor (efferent, both somatic and autonomic)Gray matter regions of brain and spinal cord“Pinched nerves” and bulging discsAscending and descending axonal tracts in white matter not anatomically delineated.
Atlanta-Boston flightOrigin-DestinationNaming of white matter tracts…..
S 9
Explanation for Cervical and lumbar enlargements of spinal cord.
Spinal nerves named for vertebral level.
Using patient’s localization of symptoms with knowledge of dermatomes to determine which spinal nerve is affected by damage.
Epidural injections into region of cauda equina of Lidocaine-like agents to block action potentials in sensory and motor axons without risk of damage to spinal cord.
8
12
5
5
1
S 10
Homunculus = representation of body partsSomatotopy = adjacent regions of the body are representedby adjacent regions in the cerebral cortex.
S 1
DermatomesS 3
How might this information be clinically useful?
Who cares?Surgery for
chronic back pain
Cranial NervesS 4
Challenge: Identifythe deficits associatedwith damage to agiven cranial nerve.
Vision
Hearing & Equilibrium
!!!
S 5
Spinal
OnOld
Fat
Olympus’
Treeless
A
Top
Figure 6.43
Locations of neuronal cell bodies, ganglia, pharmacology of the neuromuscular junction (NMJ) at skeletal muscle (nAChR)Diagram of NMJ compared to synaptic varicosities characteristic of autonomic postganglionic axons. Locations and proximities of target cells and distributions of receptors on target cells.Somatic = excitatory only at NMJ (ex. Reduced muscle tone)Autonomic= exitatory or inhibitory depending on NTs and their receptors.
S 6
ACh & mAChR
Figure 6.44S 7
Why activation of the sympathetic division has widespread effects.
S 8
Figure 6.46
Adrenal medulla is modified sympathetic ganglion that secretes mainly EPI
Antagonist = Curare
Antagonist = Atropine
S 8
S 9
Table 6.11S 10
EmotionalThermoregulatory
mAChR
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