LECTURE 5: MEMBRANE POTENTIAL Flashcards
-Functional Units of Nervous System
-receive, process and transmit information to other cells
Neurons
Components of Neurons
-Soma
-Dendrites
-Axons
metabolic maintenance
Soma
receptive surface that brings signals from other neurons toward the cell body
Dendrites
- conduct signals away from the cell
- carry information for long distances with high fidelity and without loss
Axons (nerve fibers)
Types of Neurons
-Sensory Neurons or Afferent Neuron
-Motor or efferent Neuron
-interneuron
they are nerve fibers that transmit sensory information from the body to the brain and spinal cord
Sensory Neurons or Afferent Neuron
hey are responsible for carrying signals from the brain to the body to initiate an action
Motor or efferent Neuron
neurons that connect sensory and motor neurons in the central nervous system (CNS), including the brain and spinal cord.
Interneuron
-surface membrane of motor-neuron dendrites & soma – innervated
-Soma integrates input to initiate an action potential (AP – nerve impulse)
-AP is carried from the spike-initiating zone (near axon hillock) to the axon terminal – skeletal muscle cell or gland
Transmission of Signals in a Single Neuron
Soma integrates input to initiate an _________
action potential (AP – nerve impulse)
AP is carried from the ____________ (near axon hillock) to the axon terminal – skeletal muscle cell or gland
spike-initiating zone
Electrical potential differences across the cell membrane cause by different concentrations of K+, Na+ and Cl- ions on each side of the membrane.
Membrane Potential
Membrane potential is usually between ____ and ____ mV.
-60 and -80 mV
-fundamental property of cells resulting from an excess of negative charges on side of the plasma membrane and an excess of positive charges on the other side
-source of potential energy to move molecules across membranes
-excitable cells use changes in membrane potential as communication signals
-critical for allowing the coordinated movements of cells and organisms
Membrane Potential
Nature of Nerve Signals
-every cell has a voltage or membrane potential across its plasma membranes
-a membrane potential is a localized electrical gradient across membrane
every cell has a _______________ across its plasma membranes
voltage or membrane potential
a ____________-is a localized electrical gradient across membrane
membrane potential
What is more concentrated within a cell and what is more concentrated in the extracellular fluid?
Within cell: Anions
Extracellular Fluids: Cations
Factors (potential difference)
-Concentration gradient for an ion
-Membrane that is permeable to that ion
___________ connected to a reference electrode via a voltmeter (voltage drop across the circuit) - measures membrane potential
microelectrode
an unstimulated cell usually has a resting potential of ____
-70mV
KCl
-100mM inside
-10mM outside
NaCl
– 10mM inside;
- 100mM outside
K+
- outward movement
Na+
- inward movement
Cl-
no gradient for the movement
equal numbers of anion and cations
Electroneutral
with __________ – potassium ions move out of the cell along concentration gradient
potassium channels
potassium ions move out of the cell along concentration gradient resulting to?
region of electronegativity (inside) and electropositivity (outside)
Excess ___________ inside – draw positive charges into the cell
negative charge
as more potassium leaves the cell, the electrical force_________ to a level that balances the driving force from the potassium concentration gradient
increases
potassium ions continue to move, inward and outward fluxes exactly balance each other
equilibrium potential (E ion )
Nernst Equation
Ex = RT/zF · ln [X]out/[X]in
Goldman-Hodgkin-Katz equation:
Vm = RT/F · log Pc[C]out + Pa[A]in_
Pc[C]in + Pa[A]out
-represents the sum of the equilibrium potentials of all the relevant ions
-relative permeability of the ions
-influence of each ion over the overall membrane potential is proportional to its permeability
-e.g.
resting neurons are more permeable to potassium than the other ions
Potassium – setting the resting membrane potential of neurons
Goldman-Hodgkin-Katz equation:
Cations
K+ and Na+
Principal intracellular cation
K+
principal extracellular cation
Na+
proteins, amino acids, sulfate, and phosphate are the principal intracellular anions
Anions
Principal intracellular anions
Cl-
at resting potential the concentration of K+ is greater ______ the cell, while the concentration of Na+ is greater _____ the cell - chemical potential energy
-inside (K+)
-outside (Na+)
______________ use the energy of ATP to maintain these K+ and Na+ gradients across the plasma membrane
Sodium-potassium pumps
opening of ion channels in the plasma membrane converts _________ to _________
chemical potential to electrical potential
A neuron at _______________ contains many open K+ channels and fewer open Na+ channels; K+ diffuses out of the cell
resting potential
Anions trapped inside the cell contribute to the ____________ within the neuron
negative charge
-allow ions to diffuse across the plasma membrane
-these channels are always open
Ungated ion channels
-have the ability to generate large changes in their membrane potentials
-gated ion channels open or close in response to stimuli
-opening or closing of ion channels alters the membrane ‘s permeability to particular ions, which in turn alters the membrane potential
excitable cells
open or close in response to stimuli
Gated ion channels
Types of gated ions:
- Chemically-gated ion channel
- Voltage-gated ion channel
open or close in response to a chemical stimulus
chemically-gated ion channels
open or close in response to a change in membrane potential
voltage-gated ion channels
changes in membrane potential of neuron give _____ to nerve impulses
rise
Graded Potentials
-Hyperpolarization
-Depolarizations
changes in membrane potential
graded potentials
magnitude of the change in membrane potential varies with the __________________-
strength of the stimulus
Gated K+ channels open —-> K+ diffuses out of the cell —-> the membrane potential becomes more negative
Hyperpolarization
Gated Na+ channels open ——> Na+ diffuses into the cell —–> the membrane potential becomes less negative
Depolarization
What type pf grade potential is action potential?
All or Nothing Depolarization
if graded potentials sum to _____ a threshold potential is achieved it triggers an action potential
approximately -55mV
approximately -55mV is considered as
Threshold Potential
In the resting state closed voltage-gated K+ channels open slowly in response to __________
depolarization
2 gates of Voltage-gated Na+
-closed activation gates open rapidly in response to depolarization
-open inactivation gates close slowly in response to depolarization
Most voltage-gated Na+ and K+ channels are ____, but some K+ channels (not voltage-gated) are _____
-closed
-open
process in generating action potential
- Most voltage-gated Na+ and K+ channels are closed, but some K+ channels (not voltage-gated) are open
- Voltage-gated Na+ channels open first and Na+ flows into the cell
- During the rising phase, the threshold is crossed, and the membrane potential increases
- During the falling phase, voltage-gated Na+ channels become inactivated; voltage-gated K+ channels open, and K+ flows out of the cell
- During the undershoot, membrane permeability to K+ is at first higher than at rest, then voltage-gated K+ channels close; resting potential is restored
During the ___________ after an action potential, a second action potential cannot be initiated.
refractory period
The refractory period is a result of a temporary ______________.
inactivation of the Na+ channels
________ propagate themselves along an axon
nerve impulses
the action potential is repeatedly regenerated along the _______
length of the axon
An action potential is generated as _______ inward across the membrane at one location.
sodium ions flow
The_________________ has spread to the neighboring region of the membrane, depolarizing it and initiating a 2nd action potential. At the site of the 1st action potential, the membrane is repolarizing as K+ flows outward.
depolarization of the 1st action potential
A 3rd action potential follows in sequence, with _________ in its wake. In this way, local currents of ions across the plasma membrane give rise to a nerve impulse that passes along the axon
repolarization
in myelinated neurons only unmyelinated regions of the axon depolarize
thus, the impulse moves faster than in unmyelinated neurons
Saltatory conduction
action potential travels directly from the presynaptic to the postsynaptic cells via gap junctions
Electrical Synapses
-more common than electrical synapses
-postsynaptic chemically-gated channels exist for ions such as Na+, K+, and Cl-. Depending on which gates open the postsynaptic neuron can depolarize or hyperpolarize
Chemical Synapses
a region where neurons nearly touch and where nerve impulse is transferred
synapse
Small gap between neurons
synaptic cleft
Transmission across a synapse is carried out by________
neurotransmitters
Process of transmission across synapse that is carried out by neurotransmitter.
- Sudden rise in calcium at end of one neuron
- Stimulates synaptic vesicles to merge with the presynaptic membrane
- Neurotransmitter molecules are released into the synaptic cleft
Primary Factors Influencing Impulse Transmission
-Axon diameter
-Myelination
-Temperature
velocity of impulse propagation varies as a function of ________________
axon diameter and myelination
how fast the membrane ahead of the active region is brought to threshold by the local-circuit current
conduction velocity of AP
the greater the length constant (distance along a cell over which a potential change decays in amplitude by 63%) the ______ the conduction velocity of AP
faster
Evolutionary adaptation to increase length constant
- invertebrates - increase in axonal diameter (reduces the internal longitudinal resistance)
-Vertebrates – myelination
increase the transmembrane resistance and decrease the effective neuronal membrane capacitance
Myelination
when the number of membrane layers wrapped around the axon _____________
Resistance increases (cytoplasm and extracellular fluid)
when myelin layer in very thick
Capacitance decreases
less capacitative current is required to change the _____; more charge can flow down the axon to depolarize the next segment
Membrane Potential (Vm)
Change in resistance and capacitance – increases the length constant = ________________
enhancing the efficiency with which longitudinal current spreads
specialized intercellular spaces between a neuron and an effector cell or another neuron
Synapses
-direct ionic coupling
-plasma membrane of pre- and post-synaptic cells are in close apposition and coupled by protein structures – gap junctions – where electrical current flow directly from one cell into the other
- electrical signal is similar although attenuated
Electrical synapses
plasma membrane of pre- and post-synaptic cells are in close apposition and coupled by protein structures – _________ – where electrical current flow directly from one cell into the other
gap junctions
-transient change in the Vm of the cell
-spreads thru gap junctions into cell B (change in Vm)
-Potential change is lower in B because of potential drop as the current crosses the gap junctions
subthreshold current in cell A
________________ action potential might not elicit an action potential in the postsynaptic cell (less common)
Single presynaptic
Purely electrical means process (without intervention of a chemical transmitter)
Rapid
Electrical synapsis is effective in?
-effective in the synchronization of electrical activity within a group of cells
-Effective for rapidly transmitting information across a series of cell-cell junctions
Kinds of Synapses
-Electrical Synapses
-Chemical Synapses
-signals in the pre- and postsynaptic cells are linked by chemical neurotransmitters.
-slower transmission than electrical synapse
-time lag occurs
-AP may flucturate
-mediated by neurotransmitters (from terminal bulb of presynaptic axon)
Chemical Synapses
Chemical Synapses type of transmission
- Fast Chemical Transmission
- Slow Chemical Transmission
-neurotransmitters (small molecules) are synthesized in the terminals and stored in small clear vesicles
-Transmitters - released by exocytosis into the synaptic cleft
-Transmitters – act on ligand-gated channels in the post synaptic membrane
Fast Chemical Transmission
-Transmitters are usually larger molecules (amines and peptides)
-Onset of postsynaptic response is slower (hundreds of milliseconds) and can last longer (seconds to hours)
-Vesicles are larger and synthesized in the cell body and transported to the nerve terminal
-Neurotransmitters are released far from where fast neurotransmitters are released
-Transmitters act indirectly through G protein linked receptors to modify channels and other intracellular processes
Slow Chemical Transmission
Chemical Synapse: Single neurons may produce ______ kinds of transmission
both
Single transmitter may affect postsynaptic neurons by means of ________and_____________
ligand-gated channels and G-protein-coupled receptors
Synaptic effects can either be _______or ________
excitatory or inhibitory
axon of terminals of presynaptic neurons _______ (lie in longitudinal depression)
bifurcates
Muscle membrane lining the depression form ____________ (1-2 um interval)
junctional folds
above the junctional folds are the __________ (with many synaptic vesicles)
active zones
Cleft with _____________ that “glues” pre and postsynaptic membranes
mucoplolysaccharide
where vesicles are released by exocytosis
Active zones
_____________ diffuse down Active zones concentration gradient to the postsynaptic membrane
Neurotransmitters
Example of Chemical Synapses
Acetylcholine
-generated during transmission of a nerve impulse across a synapse
-graded, with longer duration but lower amplitude (unlike AP which is all-or-none)
-spreads passively and decays with distance
-magnitude related to amount of neurotransmitter released
Synaptic Potentials
Ionic current that flows across a postsynaptic membrane when ion channels open after a neurotransmitter molecules bind to membrane receptors
Synaptic current
The same neurotransmitter can produce different _____ in different types of cells
effects
Five Major classes of neurotransmitters
-Acetylcholine
-Biogenic Amins
-Amino Acids
-Neuropeptides
-gases
Criteria for a Neurotransmitter
-If the candidate substance is applied to the membrane of a postsynaptic cell, it must elicit precisely the same physiological effects in the postsynaptic cell as does presynaptic stimulation
-Must be released during activity of the presynaptic neuron
-action of the substance must be blocked by the same agent that block natural transmission at that synapse
-Modify the conductance of ion channels
-Act directly on ion channel proteins to change conductances through the postsynaptic membrane = change in Vm (direct or fast synaptic transmission)
-Biochemical pathway within the postsynaptic cell – change in the state of membrane-associated or cytosolic second messengers = change in ion channel proteins – shift in Vm occur more slowly (slow or indirect synaptic transmission)
Neurotransmitter
neurotransmitters that act indirectly; modify the behavior of many postsynaptic neurons at once
Neuromodulators
Types of Neurotransmitter
-Neuropeptide (Larger molecules like amino acid)
-Small molecules
Acetylcholine
Site of Action:
- Vertebrate NMJ (Action: Excitatory)
-Vertebrate autonomic nervous system: pre-to postganglionic neurons (Action: Excitatory)
-Parasympathetic neurons (Excitatory or Inhibitory)
-Vertebrate CNS (Excitatory)
-Many Invertebrates (Excitatory or Inhibitory)
Norepinephrine
Site of Action:
-Vertebrate postganglionic sympathetic neurons (Excitatory or Inhibitory)
-Vertebrate CNS (Excitatory or Inhibitory)
Glutamic Acid
Site of Action:
-Vertebrate CNS (Excitatory)
-Crustacean CNS and PNS (Excitatory)
y-Aminobutyric Acid (GABA)
Site of Action:
- Vertebrate CNS (Inhibitory)
-Crustacean CNS and PNS (Inhibitory)
-Annelid CNS and PNS (Inhibitory)
Serotonin (5-hydrocy-tryptamine)
Site of Action:
-Vertebrate and Invertebrate CNS (Inhibitory, Modulatory)
Dopamine
-Vertebrate, annelid, arthropod CNS, PNS or Both (Excitatory or Inhibitory (?)
Glycine
Site of Action:
-Vertebrate Spinal Cord (Inhibitory)
Neurotransmitter: Biogenic Amines
-Norepinephrine
-Dopamine
-Serotonin
Neurotransmitter: Amino Acid
-GABA (Gamma (y)-aminobutyric Acid)
-Glutamate
Neurotransmitter: Neuropeptides
-Substrate P
-Met-enkephaline (an endorphin)
Neurotransmitter: Gases
Nitric Oxide
Types of Neurotransmitter based in transmission
A. Fast, Direct Transmission
B. Slow, Indirect Transmission
- acetylcholine, glutamate aspartate, ATP – fast excitatory synaptic transmission
-γ- Aminobutyric acid and glycine – mediate fast inhibition
Fast, Direct Neurotransmission
Example of Fast Direct Neurotransmitter
Acetylcholine
What releases Acetylcholine?
Cholinergic neurons
Acetylcholine in Vertebrates
motor neurons, pregangionic neurons of ANS, postganglionic neurons of the parasympathetic ANS, CNS
Acetylcholine in Invertebrates
molluscan CNS, motor neurons of annelids, sensory neurons of arthropods
Molecules with crucial structural features in common with neurotransmitters can act on their ________
synapses
molecules that mimic the action of a neurotransmitter (carbachol)
Agonists
molecules that block the action of a neurotransmitter (D-tubocurarine)
Antagonists
-Hydrolysis to ____________ and acetate by acetylcholinesterase (AChE – synaptic cleft)
-__________ - reabsorbed by the presynaptic membrane and recycled
choline
Condensation with acetylCoA to form ________
new Acetylcholine
___________________ – ACh lingers in the cleft and concentration increases; postsynaptic cell cannot repolarize; ACh become inactivated (respiratory muscle paralysis)
Block AChE (sarin gas, insecticides)
released at excitatory synapses in vertebrate CNS and at fast excitatory neuromuscular junctions (insects and crustaceans)
Glutamate
-transmitter at inhibitory motor synapses (crustaceans and insects) & inhibitory transmitter in vertebrate CNS , peripheral and enteric nervous systems (Parkinson’s disease)
-decreases with Parkinson’s; Baclofen – relieves tremors
- reduces sensitivity of muscle cell to stimulus;
GABA
Examples of Slow, Indirect Neurotransmitters
- Norepinephrine
- Epinephrine
3.Adrenergic Neurons
excitatory transmitter released by the postganglionic cells (vertebrate sympathetic system)
Norepinephrine
_______________ and ______________ have similar structure & pharmacological action
Epinephrine and norepinephrine
use epinephrine or norepinephrine as transmitters
Adrenergic Neurons
excitatory or inhibitory (postsynaptic membrane)
Epinephrine
-Synthesized from amino acid phenylalanine
-Inactivated:
-Taken up into the cytoplasm of the
presynaptic neuron –repackaged into
synaptic vesicles for rerelease
-Monoamine oxydase (MAO)
-Deactivated by methylation within the
synaptic cleft
Norepinephrine
Some psychoactive drugs have similar molecular structures with ___________, which allows them to act at synapses
biogenic amines
psychoactive drug that induces hallucinations by interfering with norepinephrine (its analog
Mescaline
(mimics norepinephrine) and cocaine (interferes with the inactivation of norepinephrine) – interacts with adrenergic neurotransmission
Amphetamines
Important for nervous and muscular response
Propagation of Action Potential
-Where integration takes place
-associated with sensory receptor and effector
Central Nervous System (CNS)
3 basic function of CNS
-Reception of sensory input
-Integration
-Motor output
What produces myelin sheath?
-Oligodendrocytes
-Schwann Cells
Soma=_____
Cell Body
Where does action potential is propagated?
Axon Hillock
Propagation of action potential is more efficient with ___________
Myelinated Axon
