Martini Chapter 12 Bio 103 Part 2 Nervous Tissue Martini Chapter 12 Bio 103 Part 2

How do neurons communicate? Electrically: Action Potentials All or Nothing ALWAYS EXCITATORY!

How do neurons communicate? Electrically: Action Potentials All or Nothing ALWAYS EXCITATORY! Chemically: Neurotransmitters various types can stimulate or depress electrical activity can have long impact on post synaptic cellular function

Electricity Terminology Voltage potential energy generated by separated charge Current the flow of electrical charge from one point to another Resistance hindrance to the current insulators = high resistance conductors = low resistance

Electricity Terminology Voltage potential energy generated by separated charge Current the flow of electrical charge from one point to another Resistance hindrance to the current insulators = high resistance conductors = low resistance Ohm’s Law Current (I) = voltage (V) / resistance (R) OR V = I x R

The Transmembrane Potential All cells have a difference in charge across their membranes resulting in potential energy. measured in voltage mVolts

An Analogy Membrane Potential is like a damned up lake, except, instead of water trying to get through, its ions.

The Transmembrane Potential All cells have a difference in charge across their membranes resulting in potential energy. GENERALLY: extracellular fluid is high in Na+ high in Cl-

The Transmembrane Potential All cells have a difference in charge across their membranes resulting in potential energy. GENERALLY: extracellular fluid is high in Na+ high in Cl- intracellular fluid is high in K+ high in proteins (A-)

The Transmembrane Potential All cells have a difference in charge across their membranes resulting in potential energy. THUS, the intracellular environment is relatively more negative neurons usually -70 mV at rest

The Resting Membrane Potential The voltage across the membrane when the cell is at rest. RMP for neurons usually around -70 mV

How is the Transmembrane Potential Created and Maintained? If the cell membrane were freely permeable, diffusion would eventually distribute the ions and proteins evenly across the membrane.

How is the Transmembrane Potential Maintained? If the cell membrane were freely permeable, diffusion would eventually distribute the ions and proteins evenly across the membrane. BUT: Ions must pass through ion channels or be transported by an active (ATP requiring) mechanism the large, mostly negative proteins inside the cell cannot cross the selectively permeable membrane

How is the Transmembrane Potential Created? Passive forces create voltage across the membrane, which the cell uses as potential energy: Chemical Gradient concentrations of a molecule differ across the membrane molecules diffuse to the areas of lower concentration Electrical Gradient charge differs across the membrane opposites (+/-) attract, molecules diffuse towards opposite charge Electrochemical Gradient the sum effect of electrical and chemical forces

How is the Transmembrane Potential Created? The electrochemical gradients of Na+ and K+ are the primary factor determining the transmembrane potential in neurons

How is the Transmembrane Potential Created? The electrochemical gradients of Na+ and K+ are the primary factor determining the transmembrane potential in neurons Na+ and K+ must cross the cell membrane through channels, or via active transport

Ion Channels leaky (passive) ion channels ions can always pass through these protein channels both Na+ and K+ have leak channels in neurons, but K+ has significantly more

Ion Channels gated ion channels these channels open and let ions pass only under specific circumstances

Ion Channels chemical-gated channels regulated by chemical signals that bind to the channel

Ion Channels voltage-gated channels regulated by changes in voltage across the membrane

Ion Channels mechanical-gated channels regulated by changes in pressure

Ion Channels and Chemical Gradients Na+ Na+ Na+ Na+ K+ Which direction will Na+ or K+ move through leak or gated channel? Na+ K+ K+ NEURON K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+

The membrane is more permeable to K+ relative to Na+ NEURON K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+

The membrane is more permeable to K+ relative to Na+ Potassium leaves faster than sodium enters, and the cell become more negative. Na+ K+ K+ NEURON K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+

The membrane is more permeable to K+ relative to Na+ Potassium leaves faster than sodium enters, and the cell become more negative. This is one factor that contributes to the transmembrane potential. Na+ K+ K+ NEURON K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ Na+ Na+

Electrochemical Gradient of K+ chemically K+ wants OUT A LOT electrically K+ want IN A Little together, the net effect is to move out of the cell

Electrochemical Gradient of Na+ chemically Na+ wants IN A LOT electrically Na+ want IN A Little together, the net effect is to move into the cell

Equilibrium Potential The transmembrane potential at which there is no net movement for a specific ion the voltage at which the gradient for an ion is eliminated potassium = -90 mV close to resting membrane potential sodium = +66 mV far from resting membrane potential

Maintaining the Resting Membrane Potential AT REST: cell is highly permeable to K+ large positive charge leaves the cell cell has little permeability for Na+ only slight positive charge enters cell HOWEVER, eventually enough Na+ will leak across to eliminate the resting membrane potential (-70mV)

Maintaining the Resting Membrane Potential In order to maintain the electrochemical gradients of Na+ and K+, they must be actively transported across the membrane

The Sodium-Potassium Exchange Pump

The Sodium-Potassium Exchange Pump The exchange pump maintains the electrochemical gradients for sodium and potassium, thus maintaining the resting membrane potential.

Overview of Resting Potential

Overview of Resting Potential membrane is highly permeable to K+, so the RPM is close to K+ equilibrium potential

Overview of Resting Potential membrane is not very permeable to NA+, so RMP is not close to NA+’s equilibrium potential

Overview of Resting Potential the sodium-potassium exchange pump maintains the RMP 3 NA+ out 2 K+ in

Overview of Resting Potential at rest, the passive and active transport mechanisms are in balance and the RMP is stable neuron usually -70 mV

When a neuron is excited It’s membrane potential changes 3 states of membrane potential resting potential at rest (-70 mV) graded potential some excitation (-69 to -61 mV) action potential excitation above threshold (-60 to -55 mV)

TERMINOLOGY EXCITATION INHIBITION when potential is made more positive (from -70mV to a more positive #) it is called depolarization when resting potential (-70mV) is restored after depolarization it is called repolarization INHIBITION if potential is made more negative (from -70mV to a more negative #) it is called hyperpolarization.

How Do Changes in Membrane Potential Occur? Gated Ion Channels open and close

Graded Potentials excitation or depolarization of the transmembrane potential that doesn’t spread far from the site of stimulation The stimulation was not strong enough to cause an action potential

An example of Graded Potential The neuron begins at rest

An example of Graded Potential a chemical (e.g., Acetylcholine), binds to its receptor on a chemically-gated Na+ channel

An example of Graded Potential Na+ rushes into the opened channels, causing a local current, depolarizing portions of the membrane

4 Characteristics of the Graded Potential membrane potential is most impacted at the site of stimulation change in charge only spreads locally (local current) change in voltage can be: depolarizing e.g., if Na+ channels open hyperpolarizing e.g., if K+ channels open

Graded Potentials: actual terminology Excitatory Postsynaptic Potential (EPSP) Inhibitory Postsynaptic Potential (IPSP) At any point in time a neuron may be receiving numerous EPSP’s and IPSP’s It is the summation of these individual inputs that determines if a neuron will send a message in the form of an action potential

Action Potential propagated excitation of the transmembrane potential chain reaction of depolarizing events neurons receives enough stimulation (graded potentials) to cross a threshold of voltage If the threshold is exceeded voltage-gated Na+ channels open Na+ rushes into the cell setting of the chain reaction that is an action potential

Action Potential is ALL-OR-NONE An action potential only happens if enough excitatory stimulation occurs to bring the transmembrane potential above a threshold Membrane Potential (mV) Time (ms) 1 2 3 4 5 6 7 8 -70 -55 30 threshold Threshold typically -60 to -55 mV Threshold is the voltage that opens the voltage-gated Na+ channels

Action Potential is ALL-OR-NONE Once the threshold voltage is exceeded an action potential will take place Action potentials have only 1 level of strength The amount that the threshold is exceeded will not affect the strength or speed of an action potential Membrane Potential (mV) Time (ms) 1 2 3 4 5 6 7 8 -70 -55 30 threshold action potential

Generation of an Action Potential stimulation ABOVE threshold increased Na+ permeability causes depolarization decreased Na+ AND increased K+ permeability cause repolarization prolonged increase in K+ permeability causes undershoot (hyperpolarization) return to normal membrane permeability and RMP Membrane Potential (mV) Time (ms) 1 2 3 4 5 6 7 8 -70 -55 30 threshold

Step 1 Stimulation of a Resting Neuron via excitatory chemicals binding to receptors on the post-synaptic neuron post-synaptic pre-synaptic

Step 2: Voltage-Gated Na+ Channels Open At rest, the voltage-gated Na+ channels are closed.

Step 2: Voltage-Gated Na+ Channels Open DEPOLARIZTION PHASE: When a neuron is stimulated above threshold (-60 to -55 mV) voltage-gated Na+ channels open and Na+ rushes INTO the cell making it even more positive.

Step 3: Na+ channels are inactivated and K+ channels open REPOLARIZATION PHASE At the peak of the action potential curve (~30 mV), the inactivation gate (ball) on the Na+ channel snaps shut, stopping the rush of Na+ into the cell. As long as this gate is shut, the neuron cannot fire another action potential. It is in a REFRACTORY PERIOD

Step 3: Na+ channels are inactivated and K+ channels open REPOLARIZATION PHASE At the same time, voltage-gated K+ channels are opening, allowing K+ to rush out of the cell. at 30 mV, both electrical and chemical gradients favor K+ movement out of the cell.

Step 4: Return to Normal Permeability HYPERPOLARIZATION PHASE a.k.a. undershoot K+ channels remain open beyond the point of reaching -70 mV causing an undershoot of the RMP to about -90 mV (equilibrium of K+). When the membrane potential reaches -70mV, the inactivation gate on the Na+ channel (ball) snaps back open

Step 4: Return to Normal Permeability Eventually the voltage-gated K+ channels close and the membrane is again at the RMP of -70 mV.

The Refractory Period There is a period after an action potential when a neuron cannot (1), or is unlikely (2) to produce another action potential.

The Refractory Period Absolute Refractory Period: As long as the Na+ channel is deactivated, the neuron cannot fire another action potential.

The Refractory Period Relative Refractory Period: At this point the deactivation gate on the sodium channels has reopened, and the neuron can technically produce another action potential. HOWEVER: it has to overcome the membrane hyperpolarization! Threshold = -60 mV RMP = -70 mV Hyperpolarized membrane = -90 mV

Na+/K+ exchange pump and Action Potentials 1 action potential does not change ionic concentrations enough to require the pump to reset the RMP However, a neuron can fire as many as 1000/second Thus, the exchange pump is necessary to maintain RMP

Action Potential Overview

Comparing Graded Potentials and Action Potentials

Action Potential Propagation Unlike graded potentials, action potential spread across the entire neuron from soma to synapse. continuous propagation (axon is unmyelinated) saltatory propagation (axon has myelin – see picture below)

Continuous Propagation (unmyelinated axon) action potential in initial segment local current depolarizes adjacent membrane

Continuous Propagation (unmyelinated axon) another action potential fires in this region, while the initial segment enters a refractory period

Continuous Propagation (unmyelinated axon) a local current depolarizes the adjacent portion of the membrane…and so on…..

Saltatory Propagation (myelinated axon) An action potential fires in the initial segment of the neuron.

Saltatory (leaping) Propagation (myelinated axon) The adjacent node is depolarized, skipping the myelinated segment.

Saltatory (leaping) Propagation (myelinated axon) an action potential fires in node 1 the process, with action potentials being fired at each node Because saltatory propagation leaps across internodes that may be 1-2 mm apart, propagation is much faster and consumes less energy (i.e., fewer Na ions have to be pumped back out).

Animation of Propagation

Axon Diameter and Propagation Speed Larger diameter = faster propagation less membrane/surface area to impede flow of current Squids have GIANT axons (100 X’s diameter of humans), to help them propel away from predators.

Axons are classified by diameter, myelin, and speed Type A fibers diameter of 4-20 mm myelinated 300 mph propagation speed Type B fibers diameter of 2-4 mm 40 mph propagation speed Type C fibers diameter of 2 mm or less unmyelinated 2 mph propagation speed

Type A Fibers What do they do? Carry sensory information to CNS position, balance, delicate touch and pressure Carry motor commands to the skeletal muscles

Type B and C Fibers What do they do? Carry sensory information to the CNS: temperature, pain, general touch and pressure Carry motor output information to smooth and cardiac muscles:

Why aren’t all fibers Type A? Compromise between speed and size only 1/3 of fibers are myelinated Critical information is carried over Type A