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Neurophysiology
The study of life processes of neurons
A resting neuron is?
polarized, difference in electrical charge between the inside and outside of the cell.
The inside is more (-) than outside.
resting membrane potential of a neuron is what?
-70mV
-the electrical voltage across a a cell membrane when it is at rest
Every neuron is surrounded by a cell membrane which is a ________ ___________.
Lipid bilayer
ion channels
Proteins along the membrane that allow ions and hydrophobic molecules like water to pass in and out.
Types of ion channels in neurons
-ungated (leak - open in neurons at rest) K+
Gated, open & close in response to:
-voltage gated (axon membranes)
-ligand gated (synapses - NTs bind) chemical
-mechanically gated (sensory receptors)
Which molecules are greater outside the cell, and which inside?
Outside: Na+, Cl-, CA2+
Inside: K+, proteins
Diffusion (passive transport)
high to low concentration, along concentration gradient.
electrostatic pressure
causes ions to flow towards oppositely charged areas (electrical gradient). Needs a power source, this is where the Na+ K+ pump comes in.
equilibrium potential
The electrical charge that balances 2 opposing forces, the concentration gradient and the electrostatic pressure and corresponds to the resting potential.
sodium-potassium pump neuron
Controls how many ions can enter and leave the cell
3 Na+ can leave, while 2 K+ can enter into the cell. This helps to maintain ion concentration balance (resting potential)
neurons use energy to operate sodium-potassium pumps, 3 sodium ions out, for every 2 potassium in, what happens to potassium as a result?
1. K+ ions accumulate inside the cell and diffuse out
2. Negative charge builds up inside the cell, exerting electrostatic pressure that pulls K+ ions back in.
microelectrode inserted into a cell at rest does what?
Shows that the inside of the cell is more negative than the outside
Neurons are ______________ permeable to K+, __________ permeable to Na+, and ___________ permeable to large negatively charged proteins (anions)
Selectively: K+ can enter or leave freely. At rest they move in by electrostatic pressure, as they build up they diffuse out.
Slightly: Na+ slowly leak in
Not
The neuron cell membrane is most porous to?
K+ due to the presence of more potassium leak channels.
The resting membrane potential is most dependent on?
K+
ATP is required for maintenance of the resting membrane potential? T/F
T, the Na+/K+ pump is constantly moving Na+ out and K+ in. 3 sodium out, 2 potassium in per ATP molecule.
Diffusion is the force that pulls ions against their concentration gradient? T/F
F, Diffusion moves ions along the concentration gradient, high—> low.
graded potential
Occur in dendrites and diminish as they spread across membrane.
If a membrane reaches _______, it triggers an ________ ________ and the inside of the cell briefly becomes _________.
Threshold, action potential, positive
threshold of a neuron
(-55mV)
Depolarization
EPSP bind to receptors —> triggering the opening of voltage gated Na+ channels, Na+ enters and cell becomes less negative bringing the cell closer to threshold. Enough EPSP summate an action potential will trigger.
Hyperpolarization
IPSP bind to ligand gated ion channel which causes influx of Cl- (more negative inside), efflux of K+ out of neuron (more negative inside). Moves the membrane potential further from threshold.
all-or-none property
neuron fires at full AMPLITUDE or not at all. —Thus cannot detect increased stimulus strength.
With increased stimulus an action potential will increase in ______________.
Frequency
Axon potentials
Brief but large changes in membrane potential that originate in the axon, just after the axon hillock.
What ion is responsible for depolarization during an action potential?
Na+ -sodium influx causes depolarization
Explain why action potentials are unidirectional
Action potentials only move in one direction because of the refractory period. After an action potential, the absolute refractory period prevents another AP form occurring in that section of the axon, forcing the signal to move forward.
absolutely refractory period
All-or-none response, either the AP reaches threshold and fires or it does not fire at all. If it fires it will not fire again until sodium channels shave recovered completely.
relative refractory period
the period of time following an action potential, when it is possible, but difficult, for the neuron to fire a second action potential, due to the fact that the membrane is further from threshold potential (hyperpolarized) -stimulus must be very strong.
Which ion or ions are more concentrated outside the neuron at rest?
Na+, and Cl-
Which of the following is not a force driving ion movement? Diffusion, electrostatic pressure, gravity, or concentration gradient.
Gravity
___________ channels are always open, while _________ channels open in response to specific stimuli.
Leak, gated
Describe the all-or-none property of APs
Once threshold is reached an AP will always occur with the same magnitude, regardless of the stimulus strength.
What is the primary mechanism of action of tetrodotoxin (TTX)?
It BLOCKS Na+ channels, PREVENTING the generation of APs. TTX specifically blocks voltage-gated Na+ channels, preventing the influx of sodium ions during depolarization.
After an action potential, efflux of what ion reestablishes the membrane potential
K+
What does it mean that APs are regenerated along the axon?
Action potentials are actively propagated (regenerated) along the axon, each adjacent section is depolarized and a new action potential occurs. Action potentials can travel in only one direction because of the refractory state of the membrane after depolarization.
conduction velocity
the speed of propagation of action potentials-varies with axon diameter
node or ranvier
Gaps in myelin sheath to facilitate rapid impulse
Myelin
A sheath of insulation around the axon, formed by glial cells, which speeds conduction.
saltatory conduction
the potential traveling inside the axon, jumps from node to node
Where is the action potential generated? Why?
axon hillock, has a high concentration of voltage gated Na+ channels making it highly sensitive to depolarization (lower threshold)
What is the sequence of transmission at chemical synapses?
1. AP travels down to axon to the axon terminal
2. Voltage gated Ca++ channels open and Ca++ enters
3. Synaptic vesicles fuse with membrane and release transmitter into the cleft.
4. Transmitter binds to postsynaptic receptor -causes EPSP or IPSP
5. Transmitter may bind may bind to Presynaptic AUTORECEPTORS —decreasing release
6. After binding, neurotransmitter is inactivated by: DEGRADATION (enzymes) or REUPTAKE
*when an AP reaches the end of an axon it causes the release of a neurotransmitter into the synapse.
Reuptake
a neurotransmitter's reabsorption by the sending neuron
EPSP (excitatory postsynaptic potential)
Small local depolarization, Putin cell closer to threshold. Results from Na+ ions entering the cell making the inside MORE POSITIVE
IPSP (inhibitory postsynaptic potential)
Small local hyperpolarization, pushing cell away form threshold, resulting from Cl- ions entering the cell making the inside MORE NEGATIVE
Neurotransmitter degradation with example
Breakdown/inactivation of neurotransmitter by an enzyme. Ex: acetylcholine (ACh) is broken down by the enzyme acetylcholinesterase (AChE)
AChE inhibition = raid
Cycle from transmitter release to Presynaptic terminal
1. Transmitter release form Presynaptic neuron
2. Open Na+ ion channels in postsynaptic membrane
3. Creates depolarizing current (EPSP)
4. Which passively flows down to axon hillock
5. Trigger action potential
6. Which is conducted down the axon to the Presynaptic terminal
Ligands
Fit receptors to activate or block them: lock-and-key
endogenous ligands
neurotransmitters and hormones produced by the body
exogenous ligands
drugs and toxins from outside the body
acetylcholine receptors
A synapse that uses ACh has ligand-binding sites for ACh on neurotransmitter receptor molecules in the postsynaptic membrane
Up-regulation of receptors
Increase the number of receptors on membrane
SENSITIZATION. Ex: nicotine receptors when you start smoking.
Down-regulation of receptors
decrease in number of receptors, TOLERANCE. Ex: benzodiazepines (Valium)
electrical synapse
Ion flows DIRECTLY through large channels into adjacent neurons, with no time delay. Benefits: FASTER, allows neuron to synchronize, saves energy.
Electroencephalogram (EEG)
Graphical record of spontaneous brain-wave activity obtained through electrodes placed on the scalp and forehead. Can distinguish sleep states, and provide data for diagnosis of seizure disorders.
Seizure
Is a wave of abnormally synchronous electrical activity in the brain. The normal brain tends to be desynchronized across regions.
-can be controlled with antiepileptic meds or in severe cases surgery.
How do action potentials travel?
Initiated at the axon hillock, travel down axon. Myelin sheaths insulate the neuron and enhance AP conductance. Saltatory conduction = jumps from node to node. Sodium channels located at the nodes help to regenerate AP: depolarization—>new AP. AP only travel in one direction due to refractory state of membrane after depolarization.
Myelin cells
Schwann cells (PNS) and oligodendrocytes (CNS)
saltatory conduction helps?
Keep the strength of the signal consistent (at the same time strength prevents signal degradation)
Why do Na+ channels influence the direction of AP and not K+ channels?
K+ are leak channels, never fully closed
Na+ has phases of complete inactivation, preventing AP from moving backward
Electrical vs chemical synapses
Electrical: faster, almost instantaneous due to connection at synapse -direct flow via gap junctions. Bidirectional
Chemical: slower, NT released via synaptic cleft, unidirectional
Chemical signaling
At the synapse VOLTAGE GATED Ca++ CHANNELS are KEY in triggering synaptic vesicle fusion—> releasing NT.
NT binding to postsynaptic receptor causes EPSP or IPSP
graded potential
Sum of IPSP + EPSP (at dendrites, postsynaptic):
Once the sum reaches threshold, AP triggered.
IPSP= DIP in graph (more negative)
EPSP= PEAK in graph (more positive, not as high as AP peak)
Neurotransmitter binding
Ligands bind to a receptor, lock and key mechanism
What happens to extra NT?
Reuptake by Presynaptic neuron or degradation at synapse
Why do ions require channels to pass through membrane?
They are charged so they cannot diffuse through the lipid bilayer without channels.
What does the graph look like when recorded at the myelin sheath?
A flat line, no activity
What will conduct a signal better, large-myelinated or small-unmyelinated axon?
Large myelinated
An EPSP has a reversal potential more _________ than the AP threshold whereas an IPSP has a reversal potential more ______ than threshold.
positive and negative
What ion triggers neurotransmitter release?
Ca2+ triggers synaptic vesicle fusion
The action potential changes in amplitude. T/F
False: all-or-none principle
How do we record the intensity of a stimulus?
Frequency, the neurons will fire more or less frequently depending on the strength of the stimulus
Depolarization vs. hyperpolarization
Depolarization: resting membrane potential becomes more positive
Hyperpolarization: resting membrane potential becomes more negative
Does the cell hyperpolarize or depolarize when action potential is triggered?
Depolarized to trigger the opening of Na+ channels
What ion is most closely related to the resting membrane potential?
Potassium (K+) ion -70mV
How do electrical synapses differ in their role in fast reflexes vs. complex neural processing?
Electrical synapses are better for reflexes due to their speed, while chemical synapses allow flexibility in processing
What would be the effect of a drug that prevents acetycholinesterase from breaking down acetylcholine?
ACh levels would increase, leading to continual muscle contraction.
A patient with a demyelinating disorder experiences slowed nerve signal transmission and muscle weakness, what role does myelin play in action potential conduction?
It insulates the axon, allowing Saltatory conduction for faster signal.