Exam #2 (Lecture) Flashcards
Does current flow from positive to negative or from negative to positive?
(+) to (-)
How did Hodgkin and Huxley use the voltage-clamp method to show that changes in permeability to Na+ and K+ underlie the action potential?
Membrane potential influences permeability:
(1) When depolarized there is a transient increase in sodium conductance and a slower but more sustained increase in potassium conductance.
(2) Changes can be reversed during repolarization
Suppose you are recording action potentials from a neuron. How will the action potential be affected if you remove Na+ from the external medium? How will the action potential be affected if you remove external K+?
(1) Removal of Na++ decreases action potential
(2) Removal of K+ increases action potential
How does the voltage sensitivity of K+ conductance contribute to the action potential?
(1) Selectively permeable K+ channels that are only open during depolarization
(2) Slow K+ channel activation/deactivation
Do unmyelinated axons carry action potentials?
Yes.
What is the purpose of myelin? Explain how myelin speeds the conduction of the action potential.
(1) To increase speed of impulses along nerve fiber
(2) Speed is increased due to saltational conduction by increasing resistance, decreasing capacitance and preventing electrical signal from dissipation into surrounding tissue.
What prevents action potentials from turning around and going back up the axon?
(1) The all-or-nothing attribute of function
(2) Unique unidirectional pre-synaptic and post-synaptic terminals
(3) Refractory period
Activation
The time-dependent opening of ion channels in response to a stimulus, typically membrane depolarization.
Conduction velocity
The speed at which an action potential is propagated along an axon.
Inactivation
The time-dependent closing of ion channels in response to a stimulus, such as membrane depolarization.
Membrane conductance
The reciprocal of membrane resistance. Changes in membrane conductance result from, and are used to describe, the opening or closing of ion channels.
Myelin
The multilaminated wrapping around many axons formed by oligodendrocytes or Schwann cells.
myelination
Process by which glial cells wrap axons to form multiple layers of glial cell membrane that increase axonal conduction velocity.
nodes of Ranvier
Periodic gaps in the myelination of axons where action potentials are generated.
refractory period
The brief period after the generation of an action potential during which a second action potential is difficult or impossible to elicit.
regenerative
Dendrite, axon and/or nerve regrowth
resistance
Opposition to electrical current
saltatory
jumping action
saltatory conduction
Mechanism of action potential propagation in myelinated axons; so named because action potentials “jump” from one node of Ranvier to the next due to generation of action potentials only at these sites.
tetraethylammonium ions
A quaternary ammonium compound that selectively blocks voltage-sensitive K+ channels; eliminates the delayed K+ current measured in voltage clamp experiments.
tetrodotoxin (TTX)
An alkaloid neurotoxin, produced by certain puffer fish, tropical frogs, and salamanders, that selectively blocks voltage-sensitive Na+ channels; eliminates the initial Na+ current measured in voltage clamp experiments.
Voltage clamp method (def.)
A method that uses electronic feedback to control the membrane potential of a cell, simultaneously measuring transmembrane currents that result from the opening and closing of ion channels.
Voltage clamp technique (Steps)
(1) One electrode measures membrane (Vm) potential and is connected to voltage clamp amplifier (VCA)
(2) VCA compares Vm to desired potential
(3) If Vm differs from desired then VCA, via 2nd electrode, injects additional current into axon to bring Vm into line with desired potential
(4) Current flowing back into axon, thus across membrane, is measured
Why did Hodgkin and Huxley surmise that neuronal membranes must have ion channels?
The function of the neuron membrane under normal conditions compared to the effects of changes in sodium concentration on the action potential as well as the resolution of the ionic current into sodium and potassium currents
What is patch clamping? Explain how it can be used to show that properties of voltage-sensitive Na+ and K+ channels are responsible for the action potential.
(1) Lab technique in electrophysiology that allows for the study of single or multiple ion channels in cells.
(2) By increasing or decreasing concentrations and observing the changes
What makes the frog oocyte a useful expression system for studying ion channel proteins?
Because they are capable of expressing exogenesis (foreign origin) mRNA into proteins
Compare the responses of voltage-gated Na+ and K+ channels to depolarization. How would you expect these channel properties to affect the shape, duration and frequency of action potentials?
(1) Na+ channels open and flow in
If sufficiently large the Na+ overwhelms K+, runaway condition occurs via positive feedback
(2) K+ channels open and flow out
If depolarization is small, K+ overwhelms Na+
What is meant by the statement that ion channels and active transporters have complementary functions?
Active Transporters slowly store energy by managing ion concentration across plasma membrane and Ion Channels rapidly dissipate that energy across the plasma membrane.
What must all active transporters be able to do?
Must translocate ions against their electrochemical gradients
What experimental approaches can be used to determine which ions can pass through a particular ion channel?
The use of x-ray crystallography provides both form and functional data
There are nearly 100 genes for K+ channels. Why so many? Wouldn’t one or two be enough?
The K+ channel must be equipped with far more traits than simply opening and closing. Voltage sensing, conformational changes, selectivity and appropriate secretion interaction upon synthesis and installation into the membrane must all be genetically coded.
List major stimulus types that can gate (open or close) various kinds of ion channels.
(1) Voltage
(2) Ligand
(3) Stretching
(4) Heat
Describe briefly how each of the following can be used to learn about ion channels: X-ray crystallography Expression of mRNA in Xenopus oocyte Patch clamping Mutagenesis Toxins
(1) Provides visibly observable picture of form and function
(2) Provides in-vitro, exogenic method of study
(3) Provides electrical, ionic, exchange insight
(4) Interruption of and identity of genes
(5) Functional characteristics (efflux, etc)
What do Cl–, Ca2+, Na+, and K+ channels have in common structurally? How are they different?
(1) They are all selectively permeable
(2) They are all voltage sensitive
(3) They do otherwise differ in structure, function and distribution
Although the Na+/K+ pump is electrogenic, it makes only a minor contribution to the neuron’s resting potential. Explain why.
It is electrogenic because of the 2:3, K+:Na+, Influx:Efflux creates a current.
However, a pump is much slower than a channel so the effect is minor.
What structural features of K+ channels account for ion selectivity, voltage sensitivity, and ion conductance?
(1) Desolvation of K+ is preferable to Na+ which prefers hydration
(2) Paddle-like protein domains
(3) Alpha sub-units that form a pore
Active transporters
Proteins that actively move ions into or out of cells against their concentration gradients.
ATPase pumps
Membrane pumps that use the hydrolysis of ATP to translocate ions against their electrochemical gradients.
CACNA genes
The known 16 unique Ca++ channel genes
Co-transporter
The Na-K-Cl cotransporter a protein that aids in the active transport of sodium, potassium, and chloride into and out of cells.
Electrogenic
Capable of generating an electrical current; usually applied to membrane transporters that create electrical currents while translocating ions.
ion exchangers
Membrane transporters that translocate one or more ions against their concentration gradient by using the electrochemical gradient of other ions as an energy source.
Ion selectivity
Predilection of an ion channel to discriminate between ions based on size, charge or shape.
ligand-gated ion channels
Channel complex that allows for transport of ions upon activation by neurotransmitter upon receptor.
macroscopic currents
Ionic currents flowing through large numbers of ion channels distributed over a substantial area of membrane.
microscopic currents
Ionic currents flowing through single ion channels.
patch clamping
An extraordinarily sensitive voltage clamp method that permits the measurement of ionic currents
flowing through individual ion channels.
pore
A structural feature of membrane ion channels that allows ions to diffuse through the channel.
pore loop
An extracellular domain of amino acids, found in certain ion channels, that lines the channel pore and allows only certain ions to pass.
SCN genes
Na+ channel genes (called SCN genes) produce proteins that differ in their structure, function, and distribution in specific tissue
Selectivity filter
The part of the channel complex responsible for selective permeability
Voltage sensor
Part of channel complex that detects the potential across the membrane
voltage-gated
Term used to describe ion channels whose opening and closing is sensitive to membrane potential.
voltage-gated ion channels
Ion channels whose opening and closing is sensitive to membrane potential.
Two (2) types of summation
(1) Spatial
(2) Temporal
Summation
The addition of time and space of sequential synaptic potentials to generate a post-synaptic response
What properties did Hodgkin and Huxley think ion channels would have?
They assumed that ionic currents could be explained by a change in membrane conductance (the reciprocal of membrane resistance)
What neuronal properties did Hodgkin and Huxley not anticipate?
The sheer volume of unique ion channels
Distinguish betweeen and give example of:
(1) ATPase pumps
(2) Ion exchangers
(3) Co-transporters
(1) ATPase pumps : Require ATP : i.e. Na+ Pump
(2) Ion exchangers : No ATP, 2 ions : i.e. Na+/Ca++ Exchanger
(3) Co-transporters: No ATP : Na+/K+/2Cl- symporter
Name three (3) kinds of active transporters
(1) ATPase pumps
(2) Ion exchangers
(3) co-transporters
Which way does current flow across the membrane during the rising phase of the action potential?
Na+ in: represents inbound current
Which way does current flow across the membrane during the falling phase?
Na+ outbound: represents outbound current
Patch Clamp Methods (4)
(1) Cell-attached (Single channel voltage)
(2) Inside-out (Intracellular ligand channel)
(3) Outside-out (Extracellular binding domains)
(4) Whole-cell (Vm and I of entire cell)
Chemical Synapse Components
(1) Presynaptic terminal: Bouton
(2) Vesicles contain neurotransmitter (nt.)
(3) released via exocytosis
(4) Synaptic cleft
(5) Postsynaptic membrane
Receptors
2nd messengers (cAMP, cGMP)
Two (2) Types of Synapse
(1) Electrical (Ions)
2) Chemical (Neurotransmitters
Electrical Synapse Components
Gap junctions
6-connexons (protein channels)
pair come together between cells
permits passage of ions, ATP & 2nd messengers
Who was Otto Loewi?
The Father of Neuroscience he demonstrated the neurotransmission of acetylcholine, which he originally called “Vagusstoff”. He did this by exposing an heart chemically rather than electrically to stimulate beating.
Neurotransmitter criteria (3)
(1) Present in pre-synaptic terminal
(2) Released by depolarization and/or Ca++ dependent
(3) Specific receptor of post-synaptic membrane
Synapse
Specialized apposition between neuron and target cell (chemical>electrical)