Resting Membrane Potential Review

1. Resting Membrane Potential Review • Recall there is an unevendistribution of charged substances (mainly ions) across the cell membrane of every cell in the body which creates an electrical potential between the ICF and ECF • The ICF is negatively charged compared to the ECF whereby a typical resting membrane potential (RMP) of –70 mV is established

2. Basis of the Resting Membrane Potential • In all cells, Na+ and K+ are constantly pumped across the cell membrane by the Na+,K+-ATPase maintaining: • a high Na+ concentration in the ECF and a low Na+ concentration in the ICF • a high K+ concentration in the ICF and a low K+ concentration in the ECF • There is a constant diffusion of Na+ into the cell by: • Na+ channels that are always open (leaky) • There is a constant diffusion of K+ out of the cell by: • open K+ channels that are always open (leaky) • When a cell is at rest, the pumping of the Na+,K+-ATPase, exactly equals the diffusion of Na+ and K+ • results in a steady state condition

3. Changes in the Resting Membrane Potential • Many cells of the body use the electric potential across the cell membrane to function • the membrane potential changes from its resting value due to a change in the environment of the cell • the change in the membrane potential causes the cell to “respond” to the change in its environment • Changes in the membrane potential from resting values are due to the function ofgated ion channels • these channels remainclosed (while a cell is at rest) until a change in the environment of the cell (STIMULUS) causes them to open

4. Types of Gated Ion Channels • Gated ion channelsonly allow the diffusion of 1 (sometimes 2) type of ion across the cell membrane • Ligand-gated channels • open when a specific chemical binds to the extracellular portion of the channel • Stretch-gated channels • open when the plasma membrane is stretched • Voltage-gated channels • open when the membrane potential deviates from resting and reaches a specific voltage

5. Gated Channels • Channel types include some of the following examples • Voltage-gated Ca2+ channels • Stretch-gated Cl- channels • Voltage-gated K+ channels • Ligand-gated Na+ channels • The diffusion of any additional ions across the plasma membrane occurs at a much faster rate than the rate of pumping of the Na+,K+-ATPase • this causes the cell membrane potential to deviate from the resting value

6. Operation of a Ligand-Gated Channel Example: ligand-gated Na+ channel • Closed when a chemical is NOT bound to the extracellular portion of the channel • Na+ cannot enter the cell • Opens when a specific chemical attaches to the extracellular portion of the channel • Na+ diffuses into the cell

7. Operation of a Ligand-Gated Na+ channel

8. Deviations in the Resting Membrane Potential • The opening of a gated ion channel will allow a specific ion to diffuse down its respective gradient across the cell membrane • The membrane potential will deviate from the resting value (-70mV) based on 2 criteria: • the charge of the diffusing ion • either positive (cation) or negative (anion) • the direction of the diffusion • either into or out of the cell

9. Deviations in the Resting Membrane Potential • The ICF becomes less negative when: • a cation diffuses into the cell • an anion diffuses out of the cell • depolarization • reduces the polarity of the membrane as the membrane potential moves toward 0mV • The ICF becomes more negative when: • a cation diffuses out of the cell • an anion diffuses into the cell • hyperpolarization • increases the polarity of the membrane as the membrane potential moves further away from 0mV

10. Deviations in the Resting Membrane Potential • When the gated ion channels close, the cell membrane potential returns to its resting value

11. Gated Channels and the Membrane Potential • When gated channels open: • ions move across the cell membrane down its concentration gradient (HIGH → low) • the number of ions that move across the membrane is relatively small and thus DOES NOT CHANGEthe concentration gradient of the ion • The membrane potential deviates because each ion has a large charge associated with it • the movement of only a “few” ions creates a large change in the distribution of electric charge across the cell membrane • After the gated channels have closed, the “few” ions that diffused are quickly moved up the gradient to return the membrane potential to resting

12. Responses to Stimuli • Stimulation of various cells (receptors/sensors) in the body causes the opening of gated channels which changes in the resting membrane potential initiating an electrical impulse • ligand-gated channels are opened in taste buds by the food that is ingested • stretch-gated channels are opened in free nerve endings in the dermis of the skin when bitten by a mosquito • voltage-gated receptors are opened when your lab partner uses an electrical stimulating electrode on your arm

13. Responses to Stimuli • The electrical impulse travels from the stimulated receptor cell to an effector cell (muscle and/or gland) • A change in the membrane potential of the effector cell causes a functional change in the cell allowing for an appropriate response • the salivary glands will secrete saliva into the mouth while the tongue and muscles controlling the jaw will contract, allowing you to chew and swallow or spit out the ingested food • the muscles controlling the arm and hand will contract, allow you swat the mosquito • the muscles of the hand will contract, causing the fingers and wrist to flex

14. Neurons (Nerve Cells) • The transfer of these electrical impulses over large distances is accomplished by the cells of the nervous system called neurons • capable of: • generating/initiating an electrical impulse • sending electrical impulses very rapidly from one location in the body to another • changing the resting membrane potential of other cells within the body including: • other neurons • effector cells of the body • The nervous system is made up of millions of neurons that connect all parts of the body to one another

15. The Nervous System

16. Neuron Anatomy • Dendrites • branched appendages that receive stimuli • respond to a stimuli by opening gated channels • location of stretch or ligand-gated channels • change in the membrane potential of the neuron at the precise location of the stimulus on the cell • Body (soma) • location of organelles, but can also receive stimuli • respond to a stimuli by opening gated channels • location of stretch or ligand-gated channels • change in the membrane potential of the neuron at the precise location of the stimulus on the cell • Axon • long extension of the cell body, that can branch many times which sends the electrical impulse to other cells in the body • location of voltage-gated channels

17. Neuron

19. Initiation of an electrical impulse • The initiation of an electrical impulse occurs at either the dendrites or the body of a neuron • the opening of stretch or ligand-gated channels causes EITHER a depolarization or a hyperpolarization, depending on the charge and the direction of movement of the ion at the location of the opened gated channels • this type of membrane potential change is called a graded (local) potential • a brief, localized change in the membrane potential

20. Graded Potentials • The grade or magnitude of depolarization or hyperpolarization is directly related to the size of the stimulus • determines the number of gated channels that is opened • determines the number of ions that cross the plasma membrane

21. Graded Potentials of Stretch-gated Channels • A small pressure applied to the skin: • causes a small amount of stretch of the cell membrane of the pressure sensing cells of the skin • causes few stretch-gated channels to open • allows few ions to cross the cell membrane • causes a small change of the membrane potential from the resting value • A large pressure applied to the skin: • causes a large amount of stretch of the cell membrane of the pressure sensing cells of the skin • causes more stretch-gated channels to open • allows more ions to cross the cell membrane • causes a larger change of the membrane potential from the resting value

22. Graded Potentials • Decrease in magnitude with distance from the site of stimulation • as ions move into/out of the cell through opened gated channels, they diffuse away from the opened gated channel • as the ions diffuse away from the opened gated channel the concentration of the ion decreases • as the ion concentration decreases, so does it’s influence on the membrane potential • the further away from the stimulus, the closer the membrane potential is to the resting value

23. Function of Graded Potentials • The purpose of graded potentials in the dendrites or soma is to cause (or prevent) the opening of voltage-gated ion channels in the axon of the neuron • open when the membrane potential in the axon has been depolarized to a minimum value • the opening of voltage-gated channels in the axon will create a membrane potential change in the axon called an action potential • the action potential will “travel” down the length of the axon and all of its branches to the axon terminus

24. Action Potentials (APs) • A very rapid sequence of membrane potential changes due to the opening and closing of voltage-gated Na+ and voltage-gated K+ channels • There are 3 sequential phases to an AP in a neuron: • Depolarization • a reduction in the polarity of the membrane potential • Repolarization • a return of the membrane potential towards the resting value • Hyperpolarization • the membrane potential reaches values more negative than the resting value • All APs in a neuron have the same magnitude regardless of the size of the stimulus (not graded)

25. Action potential

26. Threshold and Action Potentials • The initiation of an AP occurs at the beginning of the axon called the initial segment and requires that the membrane potential at the axon be depolarized to threshold • the minimum amount of depolarization required to initiate an action potential • typically -55mV • causes the opening of voltage-gated Na+ channels

27. Threshold and Action Potentials • Threshold can be reached by a depolarizing graded potential in the dendrites or soma of a neuron • small (weak) stimuli DO NOT initiate an AP because the magnitude of the graded potential at the axon is TOO SMALL to depolarize the membrane at the axon to threshold • subthreshold stimuli • large (strong) stimuli DO initiate an AP • threshold stimuli • All-or-none phenomenon • action potentials either completely, or not at all

28. Na+ and K+ channels are closed Ionic Basis of Action Potential (Resting State)

29. If a strong enough stimulus is presented to the cell, the membrane potential depolarizes to threshold (-55mV) causing: Na+ channels to open Na+ enters the cell (diffusion) membrane potential continues to depolarize to +30mV K+ channels slowly begin to open Ionic Basis of Action Potential (Depolarization)

30. Membrane potential reaches peak depolarization of +30mV causing: Na+ channels to close K+ channels to open K+ exits the cell (diffusion) the membrane potential returns toward resting values (repolarization) Ionic Basis of Action Potential (Repolarization)

31. K+ channels remain open This causes more than enough K+ to leave the cell resulting in hyperpolarization of the membrane potential Eventually, the K+ channels close, allowing the membrane potential to return to resting Ionic Basis of Action Potential(Hyperpolarization and Return to Resting)

32. Refractory Periods

33. Absolute Refractory Period • The absolute refractory period: • is the time during an action potential that another action potential CANNOT be initiated • no matter how strongly the dendrites/soma are stimulated • ensures that each action potential created is separated from one another so that the body can interpret stimuli accurately • is time required for the voltage-gated Na+ channels to be “reset” • required for the channels to open again

34. Relative Refractory Period • The relative refractory period: • is the time after the absolute refractory period until the membrane potential returns to the resting value • During this time another action potential CAN be initiated • requires a stronger than normal stimulus at the dendrites • during this time some of the voltage-gated Na+ channels have been “reset” while others have not

35. Propagation of an Action Potential • Once an action potential has been initiated at the beginning of the axon, it must “travel” (propagate) along the length of the axon to the axon terminus • The influx of Na+ into the cell during depolarization causes the membrane potential in “front” of the opened Na+ channels to depolarize to threshold • Reaching threshold opens up the Na+ channels in “front” of the site of the action potential causing an action potential to be created in this new location • As the next group of Na+ channels begins to open, the ones “behind” them are closing • The impulse continues to propagate away from its point of origin to the axon terminus • “the domino effect”

36. Propagation of an Action Potential

37. Propagation Velocity of an Action Potential • The propagation velocity is the speed at which the action potential propagates along the length of the axon • Conduction velocity depends on: • axon diameter (thickness) • the larger the diameter, the greater the conduction velocity • presence of a myelin sheath • dramatically increases impulse speed • to speeds up to 300 mph • more effective than increasing axon diameter • The human body uses both methods to maximize propagation velocity

38. Myelin Sheath • White, fatty (lipid), segmented covering around most long axons • Increases propagation velocity of APs by electrically insulating the axon • Formed by Schwann cells • wraps around the axon many times with its plasma membrane • encloses the axon with many concentric layers of lipid bilayers

39. Myelin Sheath

40. Myelin Sheath Formation

41. Nodes of Ranvier • The nodes of Ranvier are: • gaps between the Schwann cells • naked axon segments • the ONLY locations of voltage-gated Na+ and K+ channels • in large densities • ONLY locations where an AP can be generated along the length of the axon

42. Saltatory Conduction • Ions pass through a myelinated axon only at the nodes of Ranvier creating an action potential • due to the large density of voltage-gated Na+ channels creates a large electrical field surrounding the node • causes the cell membrane to reach to threshold at a large distance away (the next node) • creates and AP at the next node • The action potential jumps from node to node • much faster conduction rate compared to unmyelinated axons (of the same diameter)

43. Nodes of Ranvier and Saltatory Conduction

44. Saltatory Conduction

45. Axon Termini and Synapses • When the AP reaches the axon termini the impulse must be transmitted to the next cell in the path to the effector • A synapse is the junction between 2 cells where the impulse is transmitted from one cell to another : • Presynaptic cell (before synapse) • Postsynaptic cell (after synapse) • found between: • 2 neurons • a neuron and an effector cell (muscle or gland) • 2 general types include: • chemical • electrical

46. Axon Termini and Synapses

47. Chemical Synapses • Composed of 3 parts: • axonal terminal of the presynaptic neuron • contains synaptic vesicles • filled with a neurotransmitter (chemical/ligand) • receptor region on the postsynaptic cell which contains ligand-gated channels • fluid-filled space between the cells (synaptic cleft) • separates the presynaptic and postsynaptic cells

48. Chemical Synapse

49. Synaptic Cleft: Information Transfer • An action potential that arrives at the axon terminus of the presynaptic cell causes the opening of voltage-gated Ca2+ channels • causes Ca2+ to diffuse into the cytoplasm of the presynaptic cell • triggers the exocytosis of neurotransmitters into the synaptic cleft • The neurotransmitters diffuse across the cleft and open the ligand-gated channels on the postsynaptic cell • causes ions to cross the cell membrane and result in a graded potential • postsynaptic potential • depolarization or hyperpolarization

50. Synaptic Cleft: Information Transfer