Download Action Potential

Cell Bio & Physio Lecture 3: Membrane and Action Potentials:
What is an action potential?
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An action potential is a form of electrical signal or message that the nervous system receives and transmits.
It results from the movement of ions across a membrane
Cell Transport:
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Lipid soluble molecules can directly cross the membrane whereas water soluble molecules require protein
carriers which control ion movement
Transport can be passive (facilitated diffusion, no energy needed) or active (requires energy; ion pump)
Ion channels control ion movement by responding to external stimuli and by being selective to ion shape and
charge
Channels relevant to action potential:
 Potassium and sodium voltage-gated channels:
o Controlled by a change in voltage and selective for their specific ion
 Potassium and sodium “leak” channels:
o Essentially always open and allow free passage of their specific ion
Active Transport of Ions:
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The Na+ K+ pump (uses ATP, has ATPase activity) pumps two potassiums into the cell and three sodiums out
This happens so that a chemical concentration gradient can be established for sodium and potassium AND so
that a charge imbalance is established (negative cell interior)
Purpose of the Gradients:
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Driving cellular transport processes
o Primary active transport by the Na+ K+ pump leads to a low concentration of sodium inside the cell
compared to the outside
o This allows sodium to diffuse into the cell, and the energy of its diffusion can be used to drive glucose
into the cell against its concentration gradient
Electrical excitability:
o Important for neurons and muscle fibers
o The charge difference between the inside and outside of the cell allows them to create electrical
signals and makes them excitable
Electric Principles:
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Voltage- difference in electric potential between two points that establishes an electromotive force
Electromotive force leads to a current (flow of charged particles between two points)
 In a circuit- electrons are the charged particles we are talking about
 In a cell- ions are the particles
Measuring potential: using one electrode inside the cell and one in the ECF (at zero volts)
o Typically the inside of the cell has a resting potential between -55 to -90 mV
Diffusion potential: when a charged solute particle (ion) moves down its concentration gradient (leads to a
charge imbalance)
Equilibrium potential:
o Continuation of diffusion potential
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o As the molecule moves down its concentration gradient, it gets to a point where it can’t move anymore
because the opposite charge pulls it back. This means that the diffusion force is countered by an
electrical force. Ions stop moving across membrane
Bulk Electroneutrality:
o In any solution, positive balances negative
o We get a potential when very small (one in three million) ions move across the membrane, so the bulk
electroneutrality is not disrupted.
Calculating Equilibrium potentials:
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Nernst equation: if we know concentration on either side and charge, we can calculate equilibrium potential
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Commmon Equilibrium Potentials:
o Sodium: +65 mV
o Calcium: +120 mV
o Potassium: -85 mV
o Chloride: -90 mV
Resting Membrane Potential:
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Note: Nernst equation is used to calculate potential for only ONE ion
Resting membrane potential involves all the ions AND the permeabilities across the ion channels
Recall: we need ion channels because membranes don’t allow passage of polar molecules (the resistance
would be too high and conductance would be too low)
Conductance of a certain ion depends on permeability which depend on sufficient, specific, and open channels
How to calculate resting potential? 2 equations
o Goldman equation: weighted by permeability
o Chord conductance equation: weighted by conductance
 Low conductance means the ion doesn’t really contribute to the potential
 Usually sodium and potassium have the most contribution because LEAK CHANNELS are
constitutively open
= -70 mV
(In typical
neuron)
Where does -70 mV resting potential come from?
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If potassium was the only thing present, it would be -90 mV
With sodium, it becomes -67 mV (+23 mV)
And the sodium potassium pump results in the last -3 mV which brings it to -70 mV
-67
Action Potential:
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Action potential- the ability of a cell to change its potential; potential in action.
o Only few cells can do this: neurons and muscle cells mainly
Due to the resting potential of cells, they are polarized- charge difference between inside and outside
Depolarization- decreasing the polarization (charge difference) across the membrane
 Membrane voltage becomes more positive
 If it depolarizes enough, it can cause an action potential!
Repolarization: return of the voltage to the resting value after depolarization
Hyperpolarization: increase in polarization, becoming more negative than resting potential
Voltage gated Na and K channels are what allows the changes in conductance to occur
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Absolute refractory period: (see graph above)
o The cell can’t produce another action potential because of inactivation gates on the Na channel
Relative refractory period:
o Starts at the end of the absolute refractory period
o Another action potential is possible but would need a greater than normal depolarization
current
Graded potential:
o Some stimuli are not strong enough to create an action potential but still cause some
depolarization called graded potential which is proportional to the stimulus strength
o As the graded potential propagates along the neuron, it loses strength because there aren’t
many channels around it for propagating the potential
o Only when the graded potential reaches -55 mV (DEPOLARIZATION THRESHOLD) does an action
potential occur: all or none response.
o An action potential does not lose its strength as it propagates
o Note: once the threshold is met, no matter how strong the stimulus, the SAME action potential
will occur
Poisons:
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Tetrodotoxin (TTX)- from Japanese pufferfish and scorpion toxin (ScTX)- Block sodium voltage gated channels
Lidocaine- local anesthetic that can block Na channels if not properly dosed
Propagation of action Potential:
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The action potential itself DOES NOT travel. It triggers action potentials adjacent to it. Chain reaction.
Theoretically, it starts at the axon hillock (maxium Na channel density) and proceeds away from the cell body
Factors Affecting the Action Potential:
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Axon Diameter: the larger the diameter, the less the resistance, the greater the conduction
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Myelenation: improves the impulse propagation because it insulates the axon and prevents ions from crossing
the cell (prevents current loss)
o If neurons are unmyelinated, renewal of action potential is choppy and impulse is slower.
Saltatory Conduction: myelinated portions of the axon that lack voltage gated channels can cause loss of
current!
 This problem is solved because some neurons are not myelinated all the way down. There are
areas between myelinated parts that are called Nodes of Ranvier- rich in voltage channels
where the action potential renews itself.
 Saltatory conduction is 100X faster than conduction in completely myelinated neurons and
uses less energy because action potentials only occur at the nodes of Ranvier
Synaptic Transmission:
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Synapse: where the signal propagates from one cell to an adjacent cell.
o Electrical Synapses:
 less common
 Neurons linked by gap junctions through which ions flow directly
 Quick, but not well controlled
 Important in heart and bladder (coordinated contraction of all cells)
o Chemical Synapses: KEY!
 No direct communication between cells (20 micrometers apart)
 Separation is called synaptic cleft
 Steps:
 1) electrical impulse from presynaptic cell converted to chemical signal
 2) chemical signal crosses cleft
 3) chemical signal converted by to electrical by postsynaptic cell
 Note: steps create a synaptic delay
 How is the signal transferred?
 Depolarization causes Ca channel to open and Ca to enter the presynaptic cell
 Ca triggers vesicles containing the neurotransmitter to fuse with the plasma membrane
 Neurotransmitter is expelled into the cleft and binds to the postsynaptic receptors
 They bind shortly and then dissociate and are taken back up into the presynaptic cell or
degraded or diffuse away.
Neurotransmitter Effects:
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Neurotransmitters: chemical substances that carry signal across chemical synapse
o Must be made by presynaptic cell, released on stimulation, and exogenous application mimics in-vivo
effect
o Inhibitory neurotransmitters- hyperpolarize postsynaptic cell and prevent action potential
o Excitatory neurotransmitters- depolarize postsynaptic membrane and cause action potential
Neurotransmitter Categories:
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Acetylcholineo First to be discovered
o Only one used in somatic nervous system at neuromuscular junction
o Main one used in autonomic nervous system
Amino acids
o Localized to CNS: glycine, glutamate, aspartate, GABA
Biogenic amines:
o Epinephrine, norepinephrine, dopamine, serotonin, histamine
o Made from amino acides
o Epi and norepi are key in fight or flight
o Dopamine- reward sensation
o Serotonin- deficiency associated with depression
Neuropeptides
o String of amino acids. Commonly used in pain meds
o Endorphins- natural opiates that reduce pain
o Substance P- mediator of pain
Novel messengers
o Have other established functions
o ATP, CO, NO
Types of Receptors:
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Ionotropic receptors:
o Ion channel is part of the receptor
o Initiate an action potential by opening the channel
Metabotropic receptor:
o Coupled to G proteins and activate 2nd messengers
Neuromuscular Junction:
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Synapse between motor neuron and skeletal muscle
Nerve: organ with many axons that links the CNS to various organs and carries both motor and sensory
neurons
Motor neurons branch off into axon processes that innervate muscles near the middle of the fiber where it
branches off even further into unmyelinated processes called terminal arborizations.
The ends of terminal arborizations are called boutons and each bouton forms a synapse with the muscle fiber
o 1) acetylcholine is released in the cleft and binds to nicotinic receptors (ligand gated) on postsynaptic
cell
o 2) this opens the K and Na gated channels on the receptor and cause them to enter the cell until the
potential is -50 mV – end plate potential (not 0 because other ions can also pass through )
o 3) action potential propagates through muscle fiber