Action Potentials Flashcards
Homeostasis is a relatively stable condition of the internal environment that results from ______ system actions.
Homeostasis is a relatively stable condition of the internal environment that results from regulatory system actions.
Describe the fluid distribution of an average 70 kg male:
Total body water is 42 L (about 55-60% of body weight)
Intracellular fluid (28 L):
- Main cell compartment - 26 L
- Blood cells - 2 L
Extracellular fluid (14 L)
- Plasma - 3 L
- Interstitial Fluid - 11 L
- Transcellular - <1 L
_____ is the total solute concentration of a solution regardless of the chemical composition of the solutes.
Osmolarity
Osmolarity is the total solute concentration of a solution regardless of the ______ composition of the solutes.
Osmolarity is the total solute concentration of a solution regardless of the chemical composition of the solutes.
Osmolarity is measured in ______
osmoles/L
Hypoosmotic:
Less than 275 mOsm
Isoosmotic:
275-295 mOsm
Hyperosmotic:
More than 295 mOsm
The higher the osmolarity, the _____ the water concentration
lower
If the membrane separating the compartments is _______ to water and _____ to solute, such as in a cell, the volume of the compartments can shrink or swell as water moves, but solute remains fixed.
If the membrane separating the compartments is permeable to water and impermeable to solute, such as in a cell, the volume of the compartments can shrink or swell as water moves, but solute remains fixed.
What happens to a cell when placed in a hypertonic solution?
Cell shrinks
What happens when a cell is placed in an isotonic solution?
No change in cell volume
What happens when a cell is placed in a hypotonic solution?
Cell swells
What is the Nernst equation?
Ex = (60/z) · log (xout/xin)
(units: mV)
x is an ion (Na+, K+, Cl-, Ca2+)
z is the charge of that ion
xout is the concentration of x in ECF
xin is the concentration of x in cytoplasm
When is the nernst equation not applicable?
When the membrane is permeable to more than one ion
2 major determinants of membrane potential at any given time:
Ion gradients
Relative permeability of membrane to those ions
The _____ equation applies to multiple ions and their permeabilities (to determine the resting membrane potential)
Goldman-Hodgkin-Katz equation
(don’t memorize equation)
What is the resting membrane potential for potassium?
-85 mV
What is the resting membrane potential for Na?
+59 mV
What is the resting membrane potential of neurons and skeletal muscle cells?
Between -40 to -85 mV
Ca++ channels open in the membrane of a normal mammalian cell with a resting membrane potential of -65 mV. Which of the following will occur?
A. Ca++ moves out of the cell into the extracellular fluid.
B. The membrane potential will become more negative.
C. The membrane potential will become more positive.
D. Both A & C are correct
C. The membrane potential will become more positive.
(increasing the permeability will allow Ca to enter the cell, which will move the equilibrium potential closer to the + membrane potential)
Cl- channels open in the membrane of a normal mammalian cell with a resting membrane potential of -66.6 mV. The intracellular concentration of Cl- is 9 mM; the extracellular concentration is 116 mM. Which of the following will occur?
A. There will be no net flux of Cl- into or out of the cell.
B. The membrane potential will become more positive.
C. The membrane potential will become more negative.
A. There will be no net flux of Cl- into or out of the cell.
(The resting membrane potential is at the equilibrium potential - so no net flux)
Compare/contrast the nernst and goldman-hodgkin-katz equations:
- The Nernst equation defines the equilibrium potential for a given ion gradient across a membrane permeable to only that ion.
- The Goldman-Hodgkin-Katz equation defines the membrane potential for multiple ions and their gradients across a membrane permeable to multiple ions.
Label the chart:
______ is the voltage required to get enough voltage gated-Na+ channels to open to initiate the all-or-none behavior of the action potential.
Threshold is the voltage required to get enough voltage gated-Na+ channels to open to initiate the all-or-none behavior of the action potential.
A ______ stimulus fails to fire an action potential
Subthreshold
Subthreshold stimuli are due to the opening of _____ or _______ channels.
Subthreshold stimuli are due to the opening of ligand-gated or stimulus-gated channels.
A _______ helps activate voltage gated Na channels
positive feedback loop
Describe the relative permeabilities during an action potential:
K+ channels open much more slowly than Na+, and they continue to remain open for more time than the Na channels.
Also see that as we lose the permeability to the Na channel, the permeability to the K channel keeps going and hyperpolarizes the cell.
After voltage- gated Na channels open, they will enter a state of ______, where they’re not responsive and won’t allow more Na to enter.
After voltage- gated Na channels open, they will enter a state of inactivation, where they’re not responsive and won’t allow more Na to enter.
Repolarization of the membrane potential occurs due to: (2)
- inactivation of voltage-gated Na+ channels AND
- opening of the voltage-gated K+ channels.
Because voltage-gated K+ channels close slowly, the membrane potential _______ past the resting membrane potential.
Because voltage-gated K+ channels close slowly, the membrane potential hyperpolarizes past the resting membrane potential.
Roughly how many ion molecules are moved across the membrane during an action potential?
- The movement of only a few ion molecules is responsible for the action potential.
- It is estimated that only 1 in 100,000 K+ present in the cell leaves during an action potential!
- A similar number of Na+ enters from the ECF.
(Thus the Na-K-ATPase oesn’t have to work incredibly hard to restore ionic gradients after an action potential)
Assume the extracellular concentration of Na+ is 145 mM and the intracellular concentration is 15 mM. At the peak of the action potential, what value is the intracellular concentration of Na+ closest to?
A. 145 mM
B. 15 mM
C. 80 mM
B. 15 mM
Only 1 in 100,000 molecules actually move across the membrane. This is a miniscule concentration of ions, so the intracellular concentration doesn’t really change.
The _______ period is when all Na+ channels are either open or inactivated.
The absolute refractory period is when all Na+ channels are either open or inactivated
The _______ period is when K+ permeability is elevated and some Na+ channels are still inactivated
The relative refractory period is when K+ permeability is elevated and some Na+ channels are still inactivated
_____ propagate without degradation over long distances.
Action potentials
_____ cells in the peripheral nervous system and _____ in the central nervous system myelinate axons.
Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system myelinate axons.
The wraps of myelin increase the _____ of the membrane resulting in less leakage of current out of the axon.
The wraps of myelin increase the resistance of the membrane resulting in less leakage of current out of the axon.
______ increases the speed of conduction of the action potential along the length of the axon.
Myelination
Myelination increases the speed and efficiency of AP propagation is up to ____x faster than unmyelinated axons.
Myelination increases the speed and efficiency of AP propagation is up to 50x faster than unmyelinated axons.
Define saltatory conduction:
Wave of depolarization in a myelinated axon “jumps” from node of Ranvier to node of Ranvier
The larger the diameter, the ____ the conduction velocity.
faster
The larger the diameter of the axon, the ____ the wrapping of myelin
greater
What is the initiation site for action potentials?
The axon hillock
- The axon hillock is the initial segment of axon.
- Voltage-gated Na+ channels are highly concentrated in this region of the neuron.
- Easier to depolarize membrane here.
Voltage-gated Na channels are highly concentrated at the ______
Nodes of ranvier
_______ channels are highly concentrated at the nodes of Ranvier
Voltage-gated Na channels
A
What are the two types of synapses?
Electrical (less common in the nervous system)
Chemical (most common in the nervous system)
Electrical synapses occur between a _____ and a _____
Electrical synapses occur between a neuron and another cell
______ occurs between electrical synapses, linking the cells.
Gap junctions
______ are present in the membrane of each cell which line up to form channels with 2 nm pores. These are formed by 6 _______.
Connexons are present in the membrane of each cell which line up to form channels with 2 nm pores. These are formed by 6 connexins.
What type of synapse is occuring at each site?
A chemical synapse occurs between a ____ and a ____.
A chemical synapse occurs between a neuron and a neuron.
OR
between a neuron and a non-neuronal effector cell
e.g.
–Skeletal muscle = “neuromuscular junction” (NMJ)
–Non-neural effector cell = “neuroeffector junction”
A chemical synapse is transmitted via a neuron propagating an action potential which invades the _______
A chemical synapse is transmitted via a neuron propagating an action potential which invades the axon terminal
Presynaptic features of a neuron:
Presynaptic features:
- Axon swelling
- Synaptic vesicles
- Mitochondria
- Pre-synaptic density
A rise in ____ triggers fusion of synaptic vesicles with the presynaptic membrane.
Calcium (Ca++)
An action potential arrives at the presynaptic terminal, opening ____ channels.
An action potential arrives at the presynaptic terminal, opening Ca++ channels.
Chemical synapse which links a neuron and a skeletal muscle cell = _____
neuromuscular junction
The _____ distribute at the top of the junctional folds at them NMJ while the ________ are located at the bottoms of junctional folds and on the longitudinal surface.
The Ach receptors distribute at the top of the junctional folds at them NMJ while the voltage-gated Na+ channels are located at the bottoms of junctional folds and on the longitudinal surface.
The Ach receptors distribute at the ____of the junctional folds at the NMJ while the voltage-gated Na+ channels are located at the ____ of junctional folds and on the _____ surface.
The Ach receptors distribute at the top of the junctional folds at the NMJ while the voltage-gated Na+ channels are located at the bottoms of junctional folds and on the longitudinal surface.
To enhance the action of ACh at the NMJ:
A. increase the activity of acetylcholinesterase
B. decrease the activity of acetylcholinesterase
C. decrease the Ca++ entry into the presynaptic terminal
D. block the postsynaptic receptor
B. decrease the activity of acetylcholinesterase
At the NMJ, the EPSP is called WHAT?
End Plate Potential (EPP)
What determines whether a post-synaptic response is an IPSP or EPSP?
- Neurotransmitter released
- Receptor at the post-synaptic cell
- Whether ion channels open or close (either directly or indirectly)
- Selectivity properties of channels
- Ions present and their gradients across the membrane
Example: The ACh receptor at the NMJ is a non-selective cation channel. When ACh binds its receptor, the channel opens and Na+ and K+ flow across the membrane. Because the driving force is greatest on Na+ towards its equilibrium potential, the membrane depolarizes as a graded potential.
When graded potentials exceed _____ an action potential is generated.
When graded potentials exceed threshold an action potential is generated.
When graded potentials exceed threshold a(n) ______ is generated.
When graded potentials exceed threshold an action potential is generated.
Graded potentials at the NMJ are always _____.
excitatory
Key characteristics of graded potentials:
Transient changes in membrane potential
- EPSPs move the membrane potential toward threshold for an action potential
- IPSPs stabilize or move the membrane potential away from threshold for an action potential
Amplitude of membrane potential can vary
Decays over distance
Can summate
- Spatial summation
- Temporal summation
Choice B - AA; CC
Choice C - A&B; A&C
Complete the table:
Neurotransmitter release through exocytosis of synaptic vesicle contents is regulated by WHAT
Calcium
Muscle fiber contraction in response to stimulation is regulated by WHAT?
Calcium
How is calcium removed from the neuron?
Ca/Na exchangers
Plasma membrane Ca-ATPase
SERCA pumps (Smooth ER Calcium ATPases)
An increase in intracellular Ca++ is essential for presynaptic release of neurotransmitter. Where does the additional Ca++ come from, mainly?
A. Endoplasmic reticulum
B. Sarcoplasmic reticulum
C. Mitochondria
D. Voltage-gated Ca++ channels
D. Voltage-gated Ca++ channels
If the Na+/K+ ATPase is poisoned:
A.intracellular [K+] will increase.
B.cytosolic [Ca++] will increase.
C.Intracellular [Na+] will increase.
D.B and C are correct.
E.All of the above are correct.
D. B and C are correct.
(cytosolic [Ca++] will increase and intracellular [Na+] will increase).
Within the myofiber are ______, which contain _____.
Within the myofiber are myofibrils, which contain myofilaments.
The _____ is the smallest contractile unit of the skeletal muscle
sarcomere
Triads are composed of what?
Two SR terminal cisternae and a T tubule
What is a neuromuscular junction?
A synapse between a somatic motor neuron and a skeletal muscle fiber
What is a motor endplate?
the post-synaptic region of the skeletal muscle cell at the neuromuscular junction
What is a motor unit?
All the muscle fibers innervated by one somatic motor neuron.
A somatic motor neuron may innervate more than one muscle fiber (motor unit). HOWEVER a muscle fiber is innervated by only one somatic motor neuron, in humans.
Explain what happens at an NMJ after acetylcholine has been release from the presynaptic neuron:
- Acetylcholine diffuses across synaptic cleft and binds to nicotinic acetylcholine receptor channels
- Receptor channels open increasing the permeability of subsynaptic membrane to Na+and K+
- Na+ influx exceeds K+ efflux producing a depolarizing graded potential termed the end-plate potential (EPP)
- EPP exceeds threshold and initiates muscle action potential; voltage-gated Na+ channels open as the sarcolemma depolarizes
- Muscle action potential is conducted along sarcolemma and into transverse tubules
- Voltage-gated L-type Ca++ channels in the T-tubules (DHP receptors) open; Causes Ca++ release channels (Ryanodine receptors) in SR to open
- Ca++ diffuses out of the sarcoplasmic reticulum
- [Ca++] near sarcomeres increases.
- Cross-bridges form; contraction begins
Depolarization of the sarcolemma is propagated down the T-tubules, opening the _____
DHP Receptors
In skeletal muscle contraction, mechanical coupling of DHP receptors to _______ causes Ca++ to move out of SR into cytosol
Ryanodine receptors
Calcium binding to _____ removes the blocking action of _____, allowing cross bridges binding between actin and myosin.
Calcium binding to troponin removes the blocking action of tropomyosin, allowing cross bridges binding between actin and myosin.
Calcium release from the ___ in response to a single action potential is sufficient to bind all sites on ____ to expose the actin binding sites for maximum cross-bridge binding in a skeletal muscle.
Calcium release from the SR in response to a single action potential is sufficient to bind all sites on troponin to expose the actin binding sites for maximum cross-bridge binding in a skeletal muscle.
This differs with other muscle types
Does smooth muscle have sarcomeres?
No - no Z bands, but do have dense bodies
Key points about vascular smooth muscle:
- Surrounds some blood vessels, controlling diameter of the blood vessel lumen, regulates blood flow through vessel
- Does not fire action potentials
- Under involuntary control:
- Hormones
- Neurotransmitters
- Autonomic Nervous System
- Local stimuli
Multiunit smooth muscle cells have _____ electrical coupling between cells, vs. single unit smooth muscle cells which have _____ electrical coupling between cells. Explain.
Multiunit smooth muscle cells have little electrical coupling between cells, vs. single unit smooth muscle cells which have extensive electrical coupling between cells. Explain.
Ca++ binds ____ which activates Myosin light chain kinase (MLCK)
Ca++ binds calmodulin which activates Myosin light chain kinase (MLCK)
Ca++ binds calmodulin which activates _____
Ca++ binds calmodulin which activates Myosin light chain kinase (MLCK)
_______ phosphorylates myosin leading to cross-bridge formation and thus, contraction. ______ dephosphorylates myosin causing cross bridges to uncouple and thus resulting in relaxation.
____ is active constituitively.
Myosin light chain kinase (MLCK) phosphorylates myosin leading to cross-bridge formation and thus, contraction. Myosin light chain phosphatase (MLCP) dephosphorylates myosin causing cross bridges to uncouple and thus resulting in relaxation.
MLCP is active constituitively.
Myosin light chain kinase (MLCK) ______ myosin leading to cross-bridge formation and thus, ____. Myosin light chain phosphatase (MLCP) _____ myosin causing cross bridges to uncouple and thus resulting in _____.
____ is active constituitively.
Myosin light chain kinase (MLCK) phosphorylates myosin leading to cross-bridge formation and thus, contraction. Myosin light chain phosphatase (MLCP) dephosphorylates myosin causing cross bridges to uncouple and thus resulting in relaxation.
MLCP is active constituitively.
____ muscle contraction is slow and energy efficient
Smooth muscle
- Cross-bridge activation is slow compared to skeletal muscle.*
- Smooth muscle form of myosin has a very low rate of ATPase activity relative to skeletal muscle.*
- Shortening is slower than in skeletal muscle.*
- Smooth muscle cells do not fatigue during prolonged activity due to low rate of energy utilization.*
The tension generated by a smooth muscle cell can be graded by varying ______ concentration
The tension generated by a smooth muscle cell can be graded by varying cytosolic Ca++ concentration
Elevated Intracellular Ca++ = elevated number of bound cross-bridges = elevated tension developed
______ is the most potent endogenous vasodilator known.
Nitrous Oxide
Nitric oxide produced by _______ diffuses into vascular smooth muscle cells resulting in relaxation and vasodilation
Nitric oxide produced by vascular endothelial cells diffuses into vascular smooth muscle cells resulting in relaxation and vasodilation
Nitric oxide produced by vascular endothelial cells diffuses into vascular smooth muscle cells resulting in ______ and _____
Nitric oxide produced by vascular endothelial cells diffuses into vascular smooth muscle cells resulting in relaxation and vasodilation
Ca++ entry into the cytosol of a smooth muscle cell:
A. increases nitric oxide activation of guanylate cyclase.
B. favors the actions of MLCP.
C. favors phosphorylation of MLC.
C. favors phosphorylation of MLC.
Nitrous Oxide stimulates production of ___ through soluble guanylate cyclase, which activates ____, which then stimulates the reuptake of cytosolic Ca2+ and the opening of calcium-activated _____ channels. Cytosolic Ca++ levels fall and ____ activity decreases.
Nitrous Oxide stimulates production of cGMP through soluble guanylate cyclase, which activates protein kinase G, which then stimulates the reuptake of cytosolic Ca2+ and the opening of calcium-activated potassium channels. Cytosolic Ca++ levels fall and MLCK activity decreases.
Interalated discs contain ____ and ____
Desmosomes for strength
Gap junctions for low resistance pathways for action potential spread
_______ connect atrial myocytes with other atrial myocytes
and ventricular myocytes with other ventricular myocytes
Gap junctions connect atrial myocytes with other atrial myocytes
and ventricular myocytes with other ventricular myocytes
(However, atrial myocytes are not connected to ventricular myocytes)
The atria are electrically insulated from the ventricles except at the _____.
The atria are electrically insulated from the ventricles except at the AV node.
The _____ is the only path for excitation from the atria to ventricles.
The AV node is the only path for excitation from the atria to ventricles.
AV nodal cells conduct action potentials _____.
AV nodal cells conduct action potentials slowly.
(This allows for a delay between atrial and ventricular contraction, allowing more time for ventricular filling)
What is the conduction pathway starting from the AV node?
AV node
Bundle of His
left and right bundle branches
Purkinje fibers
(rapid conduction allows action potentials to rapidly spread throughout the ventricles)
Ventricular contraction starts in the _____, then spreads to the _____.
Ventricular contraction starts in the apex, then spreads to the ventricular walls.
Are action potentials fired between heartbeats?
No - pacemaker cells are depolarizing but no action potentials are firing.
Generally, what occurs at each labeled stage?
What channels are opened/closed during phase 4 of the cardiac action potential?
IR potassium channels are open, allowing K+ to exit the cell
(also called “very leaky channels” or “inward rectifier K+ channels”)
What channels are opened/closed during phase 0 of the cardiac action potential?
Voltage-gated Na channels open
IR K channels are becoming blocked
What channels are opened/closed during phase 1 of the cardiac action potential?
Transient outward K channels open
Voltage-gated Ca channels aka L type Ca channels aka DHP receptors begin to open
Voltage gated Na channels inactivating
What channels are opened/closed during phase 2 of the cardiac action potential?
Voltage gated Ca channels aka L type Ca channels aka DHP receptors open
Delayed Rectifier K channels (DR K channels) opening
Transient outward K channels inactivating
Voltage-gated Na channels inactivated
What channels are opened/closed during phase 3 of the cardiac action potential?
Voltage gated Ca channels inavtivating
Delayed Rectifier K channels open
Transient outward K channels inactivated
During phase 1 and 2 (depolarization) of cardiac action potentials, ___ channels inactivate while ___ and ___ channels activate.
During phase 1 and 2 (depolarization) of cardiac action potentials, Na channels inactivate while Ca and K channels activate.
During phase 3 of the cardiac action potential, ___ channels inactivate and ___ channels continue to open.
During phase 3 of the cardiac action potential, Ca channels inactivate and K channels continue to open.
Cardiac action potential threshold is about ____mV
-75 mV
Explain calcium entry into the cardiac muscle cell
L-type Calcium channels are opened during phase 2 (opening during phase 1 and inactivating during phase 3). This allows for calcium to enter the cell.
Entry of calcium via these channels causes a calcium induced calcium release from the SR
Increased ______ results in greater strength of contraction.
Increased cytosolic calcium results in greater strength of contraction.
Cardiac muscle relaxation occurs when calcium is removed from the cytosol. How is calcium removed?
Sarcolemma
- Na+-dependent 2nd active Ca++ transporters (Na+/Ca++ exchanger)
- Ca++ - ATPases
- Na+/K+- ATPases
Membrane of SR
- Ca++- ATPases (SERCA pumps
SERCA pump function decreases in a cardiac ventricular myocyte. Which of the following could occur?
A. Cytosolic [Ca++] decreases.
B. Cross bridge cycling increases.
C. Ca++ binding to troponin decreases.
B. Cross bridge cycling increases.
Label the channels that are open during each stage of the pacemaker cell action potential:
Hyperpolarization-activated cyclic nucleotide-gated (HCN) aka “funny” channels are permeable to both __ and __. These open at _____ potentials and close as membrane ____ in sinoatrial node action potentials.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) aka “funny” channels are permeable to both Na+ and K+. These open at negative potentials and close as membrane depolarizes in sinoatrial node action potentials.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) aka “funny” channels are sensitive to __ and __.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) aka “funny” channels are sensitive to NE and EPI.
The ventricular action potential is ____ than than a neuronal action potential.
The ventricular action potential is slower than than a neuronal action potential.
What is the resting membrane potential for the sinoatrial node?
There is not one
