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NPB Lecture 3
Terms in this set (34)
Resting membrane potential
-All cells have membrane potential.
-The cells of excitable tissues (nerve and muscle cells) have the ability to produce rapid, transient changes in their membrane potential when excited.
-Brief fluctuations in potential serve as electrical signals.
-The constant membrane potential present in all cells when there are at rest (when not producing electrical signals) is known as the resting membrane potential.
Molecules responsible for resting potential
-The unequal distribution of a few key ions between the ICF and ECF and their selective movement through the plasma membrane are responsible for the electrical properties of the membrane.
-The ions primarily responsible for the generation of the resting membrane potential are Na+, K+, and A-.
-A- refers to the large, negatively charged, intracellular proteins.
-Two proteins determine membrane permeability, and therefore determine resting membrane potential:
1. Na+ and K+ leak channels (permeability allowed = electrical gradient/potential formed).
-Note that permeability of the ions at resting is not zero due these leak channels.
2. Na+/K+ ATPase pump - maintains concentration differences.
Na+, K+, A- ICF and ECF concentrations
-Na+ is more concentrated in the ECF and K+ is more concentrated in the ICF.
-These concentration differences are maintained by the Na+/K+ pump at the expense of energy.
-Because the plasma membrane is virtually impermeable to A-, these negatively charged proteins are found only inside the cell.
-Also, Na+ and K+ can passively cross the membrane through protein channels specific for them.
-The membrane typically has many more channels open for passive K+ traffic than for passive Na+ traffic (the membrane is more permeable to K+)
-Thus, the concentration gradient for K+ is always outward and the concentration gradient for Na+ is always inward.
Diffusion of Na+/K+ and membrane potential
-The Na+/K+ pump active transport mechanism only separates enough charges to generate an almost negligible membrane potential.
-The vast majority of the membrane potential results from the passive diffusion of K+ and Na+ down concentration gradients.
-Still, the Na+/K+ pump does indirectly contribute to generating the membrane potential by maintaining the concentration gradients of Na+/K+ (their diffusion creates differences in charge across the membrane).
Equilibrium potential for K+ (EK+)
-When K+ diffuses out of the cell via K+ leak channels along its concentration gradient, the inward electrical gradient continues to increase in strength.
-Net outward movement by diffusion of K+ is gradually reduced as the strength of the electrical gradient approaches the strength of the concentration gradient.
-When these two forces exactly balance each other, no further movement of K+ will occur.
-The potential (differences of charge across the membrane) that exists at this equilibrium is known as the equilibrium potential for K+ (EK+).
-At this point, no more net movement of K+ out of the cell would occur down this concentration gradient because of the exactly opposing electrical gradient.
Equilibrium potential restated
-Equilibrium potential is a membrane potential at which the electrical gradient directly opposes the chemical gradient.
-It can be thought of as diffusion pushing ions across a membrane while electrical attracting is attempting to pull the ion back the opposite direction.
-Because there is no net movement of the ion, it is said to be in equilibrium (electrical and chemical forces directly counter act each other).
Membrane potential sign conventions (+/-)
-The membrane potential at EK+ is -90mV.
-The sign always designates the polarity of the excess charge on the inside of the membrane.
-A membrane potential of -90mV means that the potential is of magnitude of 90mV, with the inside being negative relative to the outside.
-The equilibrium potential for a given ion with differing concentrations across a membrane can be calculated by means of the Nernst equation.
Magnitude of equilibrium potential
-The equilibrium potential is essentially a measure of the membrane potential (the magnitude of the electrical gradient) that exactly counterbalances the concentration gradient for the ion.
-The larger the concentration gradient is for an ion, the greater the ion's equilibrium potential.
-The ENa+ = +60mV
-The EK+ = -90mV
-The resting membrane potential of a typical cell is -70mV
K+/Na+ effects on membrane potential
-Neither K+ nor Na+ exists alone in the body fluids, so equilibrium potentials are not present in body cells.
-In a living cell, the effects of both K+ and Na+ must be taken into account.
-Generally, the greater the permeability of the plasma membrane for a given ion, the greater is the tendency for that ion to drive the membrane potential toward the ion's own equilibrium potential.
-Because of the amount of K+ channels, the membrane is more permeable to K+ and it influences the resting membrane potential to a much greater extent than does Na+.
Ion permeability and membrane potential
-K+ affects the membrane potential because of its permeability within the membrane.
-This occurs because if the membrane is more permeable to an ion, the more than ion will move out across a membrane.
-When K+ moves out of the cell, more negatively charged proteins aggregate toward the membrane and create an electrical gradient in an effort to "pull" the K+ back into the cell.
Establishing a resting membrane potential
-The resting membrane potential of typical nerve cell: -70mV.
-This is much closer to the equilibrium potential of K+ (EK+) than to ENa+ because of the greater permeability of the membrane to K+, but it is slightly less than EK+ because of the weak influence of Na+.
-During the establishment of resting potential, the relatively large net diffusion of K+ outward does not produce a potential of -90mV because the resting membrane is slightly permeable to Na+ and the small net diffusion of Na+ inward neutralizes some of the potential that would be created by K+ alone, bringing the resting potential to -70mV.
-At resting potential, neither K+ nor Na+ is at equilibrium.
-A potential of -70mV does not exactly counterbalance the concentration gradient for K+ (it takes a potential of -90mV to do that).
-K+ slowly continues to passively exit through its leak channels down this small concentration gradient.
-Leak channels are open all the time, permitting unregulated leakage of their chosen ion down electrochemical gradients.
-Na+ continually leaks inward down its electrochemical gradient, but only slowly due to its low permeability as a result of few Na+ leak channels.
Steady state of ion concentrations
-In spite of the presence of leak channels, the intracellular concentration of K+ does not continue to fall and the intracellular concentration of Na+ does not continue to rise because of the Na+/K+ ATPase pump.
-The Na+/K+ pump counterbalances the rate of passive leakage.
-At resting potential, the pump transports in essentially the same number of K+ that has leaked out and the same number of Na+ that has leaked in, creating a steady state condition where no net movement of ions takes place.
-In other words, the K+/Na+ concentrations remain constant due to Na+/K+ ATPase pump.
Membrane potential in nerve & muscle cells
-Nerve and muscle cells have developed a specialized use for membrane potential.
-They can rapidly and transiently alter their membrane permeabilities to the involved ions in response to appropriate stimulations, and effectively bring about fluctuations in membrane potential.
-Rapid fluctuations are responsible for producing nerve impulses I nerve cells and for triggering contraction in muscle cells.
-Neurons and muscle cells have developed a specialized use for membrane potential - they can undergo transient, rapid fluctuations in their membrane potentials, which serve as electrical signals.
-Nerve and muscle cells are considered excitable tissues because they produce electrical signals when excited.
-Neurons use these electrical signals to receive, process, initiate, and transmit messages.
-Muscle cells use electrical signals to initiate contraction.
-These electrical signals are crucial to the function of the nervous system and all muscles.
-Charges are separated across the plasma membrane, so the membrane has potential.
-Any time the value of the membrane potential is other than 0mV (in either direction) the membrane is in a state of polarization.
-At resting potential of a typical neuron, the membrane is polarized at -70mV.
-When the membrane potential moves closer to 0mV, the membrane becomes less polarized, or depolarized (the inside becomes less negative than it is at the resting potential).
-This means fewer charges are separated than at resting potential.
-This term also refers to the inside of cells becoming positive as does occur during action potentials.
-Repolarization occurs when the membrane returns to its resting potential after having been depolarized.
-Hyperpolarization occurs when the membrane becomes more polarized (the inside becomes more than it was at resting potential) with the potential moving even further from 0mV.
How changes in membrane potential occur
-Changes in membrane potential are brought about by changes in ion movement across the membrane.
-Changes in ion movement are brought about by changes in membrane permeability in response to triggering events.
-Charges can cross the membrane only through channels specific for them or by carrier mediated transport.
-Membrane channels may be either leak channels or gated channels.
-These ion movements redistribute charge across the membrane, causing membrane potential to fluctuate.
-Gated channels can be open or closed as a result of conformational changes of the protein.
-There are four kinds of gated channels:
1. Voltage gated channels - respond to changes in membrane potential.
2. Chemically gated channels - respond to extracellular messengers.
3. Mechanically gated channels - respond to deformation such as stretching.
4. Thermally gated channels - respond to changes in temperature.
Forms of electric signals
-There are two basic forms of electrical signals:
1. Graded potentials - serve as short distance signals.
2. Action potentials - signal over long distances.
-Graded potentials are local changes in membrane potential that occur in varying grades or degrees of magnitude or strength.
-Ex. A change of membrane potential from -70mV to -60mV is a 10mV graded potential.
-Graded potentials are usually produced by a specific triggering even that causes gated ion channels to open in a specialized region of the excitable cell membrane.
-The resultant ion movement produces the graded potential (commonly the ion movement is that of Na+)
-The graded potential is confined to a small, specialized region of the total plasma membrane (the rest of membrane is still at resting potential).
-Graded potentials can initiate action potentials.
Magnitude of graded potentials
-The stronger the triggering event, the more graded channels are opened, causing a greater amount of positive charge entering the cell, which causes a larger depolarization at the point of origin (a larger depolarizing graded potential).
-Also, the longer the duration of the triggering event, the longer is the duration of the graded potential.
-Graded potentials have small spreads of depolarization because the movement of charge (Na+ ions) dwindles away as the Na+ interact with intracellular anions.
-Thus, the Na+ are neutralized as they spread, and unless there are many Na+ present (unless many Na+ channels present) they are neutralized before reaching voltage gated Na+ channels.
-Any flow of electrical charges is called a current.
-By convention, the direction of current flow is always expressed as the direction in which the positive charges are moving.
-Current is carried by ions and can move across the membrane only through ion channels.
-Current is lost across the plasma membrane as charge-carrying ions in the form of K+ leak out through parts of the membrane that have K+ leak channels.
-Because of this current loss, the magnitude of the local current (and thus the magnitude of the graded potential) progressively diminishes the farther it moves away from the initial activation area (the spread of a graded potential gradually decreases).
-Action potentials are brief, rapid, large (~100mV) changes in membrane potential during which the potential actually reverses, so that inside of the excitable cell transiently becomes more positive than the outside.
-A single action potential involves only a small portion of the total excitable cell membrane.
-Unlike graded potentials, action potentials are conducted (propagated) throughout the entire membrane and do not diminish in strength as they travel from their site of initiation throughout the remainder of the cell membrane (long distance signaling).
-During transmission, the signal does not weaken or die off, but is preserved at full strength from beginning to end.
Initiation of action potentials
-If a graded potential is large enough, it can initiate an action potential before the graded change dies off.
-Typically, the region of the excitable membrane where graded potentials are produced in response to triggering events does not produce action potentials.
-Instead, passive current flow from the graded potential region depolarizes adjacent portions of the membrane where action potentials occur.
-Depolarization from the resting potential of -70mV proceeds slowly at first, until it reaches a critical level known as threshold potential.
-At threshold potential, an explosive depolarization takes place, and the inside of the cell becomes positively charged compared to the outside of the cell (usually +30-40mV peak potential).
-Just as rapidly, the membrane repolarizes, dropping back to resting potential.
-Often the repolarization goes too far, causing brief after hyperpolarization where the inside of the membrane is more negative than normal (due to slow response of K+ channels).
-The action potential is the change in potential from threshold to peak and then back to resting with a duration of 1 msec.
All or none point
-If the initial triggered depolarization does not reach threshold potential, no action potential takes place.
-Thus, threshold is a critical all or none point.
-Either the membrane is depolarized to threshold and an action potential takes place, or threshold is not reached in response to the depolarizing event and no action potential occurs.
Action potential and voltage changes
-Action potentials take place as a result of the triggered opening and subsequent closing of two specific types of channels: voltage gated Na+ channels and voltage gated K+ channels.
-Thus, action potentials are said to use conduction, segments continually produce action potentials over and over again down the plasma membrane of the neuron without the signal being diminished.
Anatomy of a neuron
-A neuron typically consists of three basic parts:
1. Cell body
-The nucleus and organelles are housed in the cell body, from which numerous extensions known as dendrites project like antennae to increase surface area available for receiving signals from other neurons.
-In most neurons the plasma membrane of the dendrites and cell body contain protein receptors that bind chemical messengers from other neurons.
-Thus, the dendrites and nerve cell body are the neuron's input zone, because these components receives and integrate incoming signals.
-This is the region where gated potentials are produced in response to triggering events.
-The axon (aka nerve fiber) is a single, elongated, tubular extension that conducts action potentials away from the cell body and eventually terminates at other cells.
-The first portion of the axon plus the region of the cell body from which the axon leaves is known as the axon hillock.
-The axon hillock is the neuron's trigger zone, because it is the site where action potentials are triggered (initiated) by the graded potential if it is of sufficient magnitude.
-After the first actions potentials at the axon hillock are conducted, they propagate across the neuron and typically end at the axon terminals.
-These terminals release chemical messengers that simultaneously influence numerous other cells with which they come into close association.
-The axon is thus thought of as the conducting zone of the neuron, while the axon terminals are thought of as the output zones of the neuron.
Location of action potentials
-Action potentials can be initiated only in portions of the membrane with abundant voltage gated Na+ channels that can be triggered to open by a depolarization event.
-Regions of excitable cells where grade potentials take place typically do not initiate action potentials because voltage gated Na+ channels are sparse there.
-Graded potentials are generated in the cell body and/or dendrites and if they have sufficient magnitude by the time they have spread to the axon hillock, they initiate an action potential to start there.
-The ability of graded potentials to initiate action potentials decreases as we move away from the axon hillock.
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