Physiology-1 Topic: «Action potential» c. b. s. N. M. Kharissova
Purpose : • to give representation about a physiological role of the potentials produced excitable tissues, to open mechanisms of an origin membrane potential.
Brief contents: • History of opening of the bioelectric phenomena. • Classification of the bioelectric phenomena and modern representation by the nature of biopotentials: • Structure and functions of biological membranes; • Membrane potential, methods of its registration. • The characteristic, an origin, mechanisms of occurrence, activity of sodium- potassium pump;
Situational problem • The giant axon of the squid was placed in an environment that its composition corresponded to extracellular fluid. During stimulation in the axon originated PD. Then the concentration of sodium ions in the environment equated with their concentration in the axon and repeated irritation. What is discovered?
The Membrane Potential • Definition: the membrane potential is the electrostatic charge on the plasma membrane. • Note: all body cells have a similar “resting” potential. – The topic of membrane potential is mainly discussed in regard to neurons and muscle cells because in these cells the membrane potential can change in ways that carry information.
Reasons for the inside negative polarity of the resting membrane potential Contributing factors: • 1. ion distributions: concentration differences • 2. the pumps that maintain ion distributions • 3. properties of the membrane: capacitance and leak channels
Ion distributions most relevant to the membrane potential inside outside
The Na+-K+ Pump: The major pump that contributes to the membrane potential
Two ways that the Na+-K+ ATPase pump can contribute to the charge on the membrane 1. This pump could be neutral as far as directly contributing to the charge on the membrane if it moved equal numbers of K+ in and Na+ out. Often, however, the pump is electrogenic, i. e. , it contributes to the inside-negativity by moving 3 Na+ out for 2 K+ in. 2. This pump is responsible for maintaining the concentration gradients for the two most important ions that determine the membrane potential.
Relevant membrane properties: resistance and capacitance • The lipid bilayer has a high electrical resistance (i. e. , charged particles do not move easily across it) and it separates two very conductive (“salty”) solutions. • The lipid bilayer is thin (about 50 Angstroms). The thinness of the membrane allows it to store a relatively large amount of charge, i. e. , have a high capacitance: very small differences in the electrical balance of charges inside the cell easily attract opposite charges to the outside of the cell.
Possible misconceptions: typical illustrations grossly underrepresent the numbers of ions, so that it seems that the cell below has more than twice as many negatively charged ions inside it as positively charged ions…
The real situation: • The charge on the membrane is generated by an extremely small charge imbalance and represents very few ions. The oppositely-charged ions clustered on the inside and outside of the membrane are such a small portion of the total number of each category of ion, that for a large neuron, if one K+ diffuses out of the cell for every 10 million K+ inside the cell, the effect is to produce a membrane potential of 100 m. V inside-negative! ( And the charge on the membrane is never that negative!)
Leak Channels Despite the overall high resistance of the membrane, some leak channels are open in the ”resting” membrane. A few of the leak channels allow Cl- through, a few allow Na+ through, but most of the leak channels are of a size that allows K+ to pass through. Given that there are leak channels, which way will each ion move through the leak channels, on average?
Basis of predictions: analyze the forces acting on the ions: • 1. The Chemical Driving Force is the concentration gradient that exists for each ion between the inside and outside of the cell. Reminder: more Na+ outside than inside, more K+ inside than outside, more anions inside than outside (but they are impermeant) more Cl- outside than inside. • 2. The Electrostatic Force is the attraction/repulsion exerted on ions by the charge on the membrane. Reminder: in the resting state, the charge on the inside of the membrane is negative, relative to the outside.
The way things look to Cl-
Chloride is often passively distributed…. . • Cl- is driven out, repulsed by the negative charge inside, but it is driven in by its concentration gradient. The result can be that Cl- is “contented” at the resting membrane potential, with its two forces balanced. • For each ion, there is a membrane potential at which there is no net force pushing the ion across the membrane. For Cl-, the resting membrane potential is often the same as Cl-’s equilibrium potential, the potential at which electrical and chemical (gradient) forces are balanced.
How do things look to Na+?
Na+ is not conflicted! • Both the concentration gradient and the internally-negative membrane potential favor entry into the cell….
What sort of potential on the membrane would be Na+’s equilibrium potential? • Since both its concentration gradient and its charge tend to force it in, we can conclude that Na+ would only be “contented” if the inside were positive enough to start to repel it, since the positive charge would build up much faster than the concentration gradient would change. (Recall that one in every 10 million K+ ions moving out of the cell can change the membrane potential by 100 m. V). For a typical cell, the Na+ equilibrium potential is +50 m. V.
Nernst Equation for equilibrium potential: the charge that the membrane would have if only that ion could cross the membrane.
The way things look to K+ • The forces on K+ are outward, down its concentration gradient, and inward, responding to the attraction of the negative interior…
The Nernst Equation: K+ Equilibrium Potential
How do all the forces governing the permeant ions sort out, to give an internally-negative membrane potential? • concentration gradient in : out K+ = 20: 1 Na+ = 1: 9 • permeability of K+ = 50 x permeability of Na+ • It turns out that the most important force is the relatively high permeability of the membrane to K+.
Conclusions: • The resting membrane potential is around -50 to -60 m. V. It is primarily determined by the existing concentration gradients and the passive permeability properties of the membrane, which favor K+. • Evidence: • You can poison the Na+-K+ pump and there is only a small change over time. • If you switch solutions between the inside and the outside of a big nerve cell a resting membrane potential of the opposite polarity will be recorded: inside-positive!
Another way to look at it: The resting membrane potential is an unequal compromise between the equilibrium potentials of Na+ and K+ K+ has an equilibrium potential of -75 m. V (so it is only somewhat out of equilibrium): The K+ Driving Force is Vm-EK+, e. g. -55 -(-75 m. V) or +20 m. V • *Na has an equilibrium potential of +55 m. V (so it is very far from its equilibrium): Na+’s Driving Force is Vm-ENa+, e. g. -55 -(+55 m. V) or 110 m. V.
The consequence of the unequal compromise: -- slowly the gradients will “run down” unless maintained by pumps • Na+ is far out of equilibrium but has few channels through which its ions can pass. • K+ is only somewhat out of equilibrium, so it does not push very hard to cross through the many channels it has. • Therefore, the constant leakage of some Na+ in and some K+ out is roughly balanced. • That is where the Na+-K+ pump comes in – to bail out the Na+ that leaks in and replace K+ ions that leak out. In cells that make heavy use of the influx of Na+ to facilitate uptake of glucose or amino acids, there is a greater need to move the extra Na+ back out, and in such cells, the 3: 2 Na-K pump ratio is seen more often.
***The Resiliency of the Resting Membrane Potential, or …How the forces that are responsible for the membrane potential oppose any change in the potential For example, what happens if some charge is “injected” into the cell? • Q. : If the charge is +, what adjustments would you expect for passive inflow/outflow of ions? • Q. : If the charge is -, what adjustments could the flow of ions across the membrane make? (This situation is different from the situation posed by David with H+ injection – in that case pumps exchange the H+ to get it out of the cell…. )
The set-up for recording membrane potentials
Membrane response to injected current After the injected current is turned off, the membrane potential moves pretty quickly to the resting level: What is going on? .
Passive Membrane Properties viewed in time and space Restoration of the membrane potential following brief perturbations depends on • 1. the intrinsic permeability properties of the membrane and • 2. the fact that the concentration gradient for each kind of ion is a proportion (e. g. , 1: 20, 9: 1) that is backed up by enormous numbers of ions of each type that are separated by the membrane.
How passive membrane properties prevent longdistance spread of an electrical signal…
Conclusion • The membrane potential is the baseline condition to which the membrane will always return if permeability conditions are unchanged. • The signaling power of the charged membrane (and the concentration gradient “batteries” that exist in the living cell) can be evoked by opening different classes of channels in the membrane…
Neural Communication Action Potential
Action Potentials • Large and rapid change in membrane potential • electrically-gated channels • EPSPs – threshold potential • Occurs in axon – triggered at axon hillock ~
AP Characteristics • • • Voltage-gated channels All or none Slow Non-decremental Self Propagated – regenerated ~
+40 0 Vm -60 -70 -80 Time
+40 0 Vm -60 -70 -80 Time
+40 0 C & E gradients drive Na+ into cell Depolarization Na+ influx Vm -60 -70 -80 Time
+40 0 Repolarization K+ efflux Vm -60 -70 -80 Time
+40 0 Afterhyperpolarization Vm -60 -70 -80 Time
Refractory Period • after AP – won’t fire again – relative & absolute • Relative – during after hyperpolarization – requires greater depolarization ~
Relative Refractory Period +40 0 Vm -60 -70 -80 Time
Absolute refractory period • Na+ channels deactivate – will not trigger AP – must reset • Ball & Chain Model ~
Na+ channel deactivation
Na+ channel deactivation
Frequency Code • Pattern = Intensity of stimulus – frequency of APs • Place = type of stimulus – Visual, auditory, pain, etc. – Brain area that receives signal – Doctrine of Specific Nerve Energies ~
FREQUENCY CODE Weak stimulus 1. Moderate stimulus 2. Strong stimulus 3.
Saltatory Conduction • Myelinated neurons – oligodendroglia & Schwann cells • Transmit long distances – APs relatively slow, regenerates – EPSPs - fast, decremental • Saltatory: combines both types of current – speed without loss of signal ~
Saltatory Conduction • Nodes of Ranvier – action potentials • Myelinated – like electricity through wire – decremental but triggers AP at next node • Safety factor - trigger AP across 5 nodes –. 2 - 2 mm apart • larger neurons farther apart ~
Saltatory Conduction Nodes of Ranvier
PSPs vs APs • Graded –Summation • longer duration –*10 -100 msec • chemical-gated • passive spread –instantaneous –decremental • All-or-none • short – 1 -2 msec • voltage-gated • propagated –slow –nondecremental
• ACTION POTENTIAL When the muscle is stimulated, a series of changes occur in the membrane potential, which is called action potential. • The action potential occurs in two phases. 1. Depolarization and 2. Repolarization.
• Depolarization • When the impulse reaches the muscle, the polarized condition (-90 m. V) is altered, i. e. the resting membrane potential is abolished. • The interior of the muscle becomes positive and outside becomes negative. • This condition is called depolarization. With other words, depolarisation is membrane potentials difference decreasing.
• Repolarization Within a short time, the muscle obtains the resting membrane potential once again. Interior of the muscle becomes negative and outside becomes positive. So, the polarized state of the muscle is re-established. This process is called repolarization. So, it is potentials difference restoration
• ACTION POTENTIAL CURVE Resting Membrane Potential The resting membrane potential is recorded as a straight baseline at -90 m. V. Stimulus Artifact (local potential) When a stimulus is applied, there is a slight irregular deflection of baseline for a very short period. This is called stimulus artifact.
• Latent Period The stimulus artifact is followed by a short period without any change. This period is called latent period, which is about 0. 5 to 1 millisecond. Firing Level or Critical Depolarization Level Depolarization starts after the latent period. Initially, it is very slow. After the initial slow depolarization up to -15 m. V, the rate of depolarization increases suddenly. The point at which, the rate of depolarization increases is called firing level
Action potential in a skeletal muscle
Scheme of measurements of the membrane resting potential with intracellular glass microelectrode (M). The second electrode (I) placed in a cage surrounding fluid
Action potential
• Neurons can respond to stimuli and conduct impulses because a membrane potential is established across the cell membrane. • In other words, there is an unequal distribution of ions (charged atoms) on the two sides of a nerve cell membrane. • This is illustrated with a voltmeter: • •
• With one electrode placed inside a neuron and another outside, the voltmeter is 'measuring' the difference in the distribution of ions on the inside versus the outside. • And, in this example, the voltmeter reads -70 m. V (m. V = millivolts). • In other words, the inside of the neuron is slightly negative relative to the outside. • This difference is referred to as the Resting Membrane Potential. • How is this potential established? •
Establishment of the Resting Membrane Potential • Membranes are polarized or, in other words, exhibit a RESTING MEMBRANE POTENTIAL. This means that there is an unequal distribution of ions (atoms with a positive or negative charge) on the two sides of the nerve cell membrane. • This POTENTIAL generally measures about 70 millivolts (with the INSIDE of the membrane negative with respect to the outside). • So, the RESTING MEMBRANE POTENTIAL is expressed as -70 m. V, and the minus means that the inside is negative relative to (or compared to) the outside. • It is called a RESTING potential because it occurs when a membrane is not being stimulated or conducting impulses (in other words, it's resting).
• A nerve cell is called a neuron and it transmits messages by the axon. • • The nucleus of a neuron is located in the cell body. Extending out from the cell body are processes called dendrites and axons. These processes serve to conduct impulses (with dendrites conducting impulses toward the cell body and axons conducting impulses away from the cell body). • •
What factors contribute to this membrane potential? • Two ions are responsible: sodium (Na+) and potassium (K+). An unequal distribution of these two ions occurs on the two sides of a nerve cell membrane because carriers actively transport these two ions: sodium from the inside to the outside and potassium from the outside to the inside. • AS A RESULT of this active transport mechanism (commonly referred to as the SODIUM - POTASSIUM PUMP), there is a higher concentration of sodium on the outside than the inside and a higher concentration of potassium on the inside than the outside.
• The nerve cell membrane also contains special passageways for these two ions that are commonly referred to as GATES or CHANNELS. • Thus, there are SODIUM GATES and POTASSIUM GATES. • These gates represent the only way that these ions can pass through the nerve cell membrane. • IN A RESTING NERVE CELL MEMBRANE, all the sodium gates are closed and some of the potassium gates are open. • AS A RESULT, sodium cannot diffuse through the membrane & largely remains outside the membrane. HOWEVER, some potassium ions are able to diffuse out.
• OVERALL, THEREFORE, there are lots of positively charged potassium ions just inside the membrane and lots of positively charged sodium ions PLUS some potassium ions on the outside. THIS MEANS THAT THERE ARE MORE POSITIVE CHARGES ON THE OUTSIDE THAN ON THE INSIDE. • In other words, there is an unequal distribution of ions or a resting membrane potential. This potential will be maintained until the membrane is disturbed or stimulated. Then, if it's a sufficiently strong stimulus, an action potential will occur.
ACTION POTENTIAL • An action potential is a very rapid change in membrane potential that occurs when a nerve cell membrane is stimulated. Specifically, the membrane potential goes from the resting potential (typically 70 m. V) to some positive value (typically about +30 m. V) in a very short period of time (just a few milliseconds). •
• What causes this change in potential to occur? The stimulus causes the sodium gates (or channels) to open and, because there's more sodium on the outside than the inside of the membrane, sodium then diffuses rapidly into the nerve cell. • All these positively-charged sodiums rushing in causes the membrane potential to become positive (the inside of the membrane is now positive relative to the outside). • The sodium channels open only briefly, then close again.
• The potassium channels then open, and, because there is more potassium inside the membrane than outside, positively-charged potassium ions diffuse out. • As these positive ions go out, the inside of the membrane once again becomes negative with respect to the outside.
• Threshold stimulus & potential • Action potentials occur only when the membrane in stimulated (depolarized) enough so that sodium channels open completely. The minimum stimulus needed to achieve an action potential is called the threshold stimulus. • The threshold stimulus causes the membrane potential to become less negative (because a stimulus, no matter how small, causes a few sodium channels to open and allows some positively-charged sodium ions to diffuse in). • If the membrane potential reaches the threshold potential (generally 5 - 15 m. V less negative than the resting potential), the voltage-regulated sodium channels all open. Sodium ions rapidly diffuse inward, & depolarization occurs.
• All-or-None Law - action potentials occur maximally or not at all. In other words, there's no such thing as a partial or weak action potential. Either the threshold potential is reached an action potential occurs, or it isn't reached and no action potential occurs. • Refractory periods: • ABSOLUTE - – During an action potential, a second stimulus will not produce a second action potential (no matter how strong that stimulus is) – corresponds to the period when the sodium channels are open (typically just a millisecond or less)
• RELATIVE - – Another action potential can be produced, but only if the stimulus is greater than the threshold stimulus – corresponds to the period when the potassium channels are open (several milliseconds) – the nerve cell membrane becomes progressively more 'sensitive' (easier to stimulate) as the relative refractory period proceeds. So, it takes a very strong stimulus to cause an action potential at the beginning of the relative refractory period, but only a slightly above threshold stimulus to cause an action potential near the end of the relative refractory period
• Impulse conduction - an impulse is simply the movement of action potentials along a nerve cell. Action potentials are localized (only affect a small area of nerve cell membrane). So, when one occurs, only a small area of membrane depolarizes (or 'reverses' potential). As a result, for a split second, areas of membrane adjacent to each other have opposite charges (the depolarized membrane is negative on the outside & positive on the inside, while the adjacent areas are still positive on the outside and negative on the inside). An electrical circuit (or 'mini-circuit') develops between these oppositely-charged areas (or, in other words, electrons flow between these areas). This 'mini-circuit' stimulates the adjacent area and, therefore, an action potential occurs. This process repeats itself and action potentials move down the nerve cell membrane. This 'movement' of action potentials is called an impulse.
Situational problem • The giant axon of the squid was placed in an environment that its composition corresponded to extracellular fluid. During stimulation in the axon originated PD. Then the concentration of sodium ions in the environment equated with their concentration in the axon and repeated irritation. What is discovered? • response • When aligning the sodium concentration on both sides of the membrane flow these ions into the cell during stimulation is absent, and PD is not arise.
Благодарим за внимание! Thanks
Скачать презентацию Physiology-1 Topic Action potential c b s N
6 потенциал действия физиология 1 2011-2012 англ.ppt