ELECTRICAL SIGNALS IN NEURONS

1.         Origin of Resting Membrane Potentials

a.         All living cells have a charge difference across their plasma membranes, the interior of the cell being more negative than on the exterior:

i.          this voltage difference across the membrane is known as the resting membrane potential.

ii.          the membrane potential of large nerve fibers when they are not transmitting nerve signals is about –90mV.

b.         The membrane potential arises due to:

i.          the different ion concentration of the intracellular & extracellular fluids.

ii.          the selective permeability of the plasma membrane to various ions.

c.         Ions, which are charged are unable to diffuse through the lipid bilayer and they must pass through ion channels in order to cross the membrane; this enables to the cell to exert control over the concentration of the ions on both sides of the membrane.

d.            Concentration of Anions:

i.          the principal anion in the extracellular fluid is CI^- .

ii.          while the principal anions inside the cells consist of negatively charged proteins and amino acids.

iii.            because of their large size, they cannot cross the membrane forms a permanent pool of internal negative charge.

e.            Concentration of Cations:

i.          the principal cation outside cells is Na⁺.

ii.          the principal cation inside cells is K⁺.

iii.         the sodium-potassium pump causes large concentration gradients for sodium and potassium across the resting nerve membrane such that:

                                    Na⁺ (inside) / Na⁺ (outside) = 0.1

                                    K⁺ (inside) / K⁺ (outside) = 35.0

f.          Hence, there is a strong concentration gradient for Na⁺ into the cell and for K⁺ to diffuse out of the cell.

g.         The membrane potential can be attributed to 3 major factors:

i.            diffusion of K⁺ from the interior to the exterior of the cell.

ii.            diffusion of Na⁺ from the exterior to the interior of the cell.

iii.         action of sodium-potassium pump.

iv.         the other ions exist in too small a concentration or are not so permeable as to contribute to the membrane potential.

2.         K⁺ Diffusion Potential

a.            Although both Na⁺ and K⁺ ions have strong concentration gradients across the cell membrane, K⁺ is the major ion contributing to the average resting membrane potential.

b.         This is due to the following:

i.          Greater concentration gradient for K⁺ than for Na⁺ (35 times as to 0.1).

ii.            presence of leak K⁺ channels which allow for K⁺ to diffuse out of the cell down its concentration gradient, making K⁺ 100 times more permeable than Na⁺ .

c.         There is a constant loss of positive charges from the cell as K⁺ exits.

d.         Due to the impermeability of the membrane to anions, they remain trapped in the cell which becomes negative with respect to the exterior.

e.         The increasing internal negativity attracts positively charged K⁺ , supporting an influx of K⁺ down the electrical gradient until it balances the efflux of K⁺ down the concentration gradient.

f.          At this point, there will be no net movement of K⁺ and the membrane potential at this point is called the Nernst Potential for K⁺ ions, which is –94mV.

3.         Na⁺ Diffusion Potential

a.            However, there is an influx of Na⁺ down its electrochemical gradient at the same time which makes the cell interior less negative than the –94mV required to balance the K⁺ concentration gradient.

b.         The Nerst potential for the membrane’s interior due to Na⁺ alone is +61mV.

c.         Using Goldman’s equation, the combined membrane potential is –86mV.

4.            Sodium-potassium pump

a.         It continually pumps 3 Na⁺ to the outside of the cell for every 2 K⁺ that is pumped into the cell’s interior.

b.         This continual efflux of positive charges from the cell due to the action of the pump creates an additional degree of negativity (about –4mV additional) on the inside beyond that which can be accounted by diffusion alone.

5.         The net membrane potential with all the 3 factors above operative at the same time is – 90mV.

6.         Nerst Potential

a.         The potential level across the membrane that will exactly prevent net diffusion of a single ion in either direction through the membrane is called the Nerst potential for that ion.

b.         The Nerst potential for any univalent ion at normal body temperature of 37 degree celsiu is given by:

                                    Electromotive force (in mV) =   61log

c.         When using this formula, assume that the potential outside the membrane remains at zero potential and the Nerst potential is the potential inside the membrane.

7.         When a membrane is permeable to different ions, the diffusion potential that develops depends on 3 factors:

a.         the polarity of the electrical charge of each ion.

b.         the permeability of the membrane to each ion.

c.         the concentration of the respective ions to the inside and outside of the membrane.

8.            Measuring Membrane Potentials

a.            Membrane potential can be measured experimentally by inserting one electrode into a cell and placing a second electrode in the extracellular fluid.

b.         By convention, the extracellular electrode serves as the ground and is set to 0mV.

c.         The relative charge inside the cell is then measured, using a voltmeter.

d.         If a chart recorder is connected to the voltmeter, a recording of the membrane potentials difference versus time is obtained.

9.            Changes in Membrane Potentials due to Ion movement

a.            Although all cells have a membrane potential, only certain kinds of cells, including neurons and muscle cells have the ability to generate active changes in their membrane potential, which are used to conduct signals.

b.         These cells are termed excitable cells or tissue.

c.            Neurons have special ion channels, called gated ion channels that allow the cell to change its membrane potential in response to stimuli that the cell receives.

d.            Although Na⁺ contributes minimally to the resting membrane potential, it plays a key role in generating electrical signals in excitable tissues.

e.         If the stimulus opens an Na⁺ channel,

i.          the influx of Na⁺ will increase and the membrane potential will become less negative.

ii.          this is called depolariztion in which the voltage decreases from the resting potential in the direction of zero voltage.

iii.         it increases the chances that a nerve impulse will be generated.

f.          If the stimulus opens a K⁺ channel,

i.          the efflux of K⁺ will increase, causing the membrane potential to become more negative.

ii.          this is called hyperpolarization in which the cell interior becomes more negative than the resting potential.

iii.         it reduces the probability that a cell will transmit an impulse.

10.            Control of Membrane permeability by Gated Ion channels

a.         There are 4 major types of ion channels in the neuron:

i.          Na⁺ channels.

ii.          K⁺ channels: of the axon open in response to depolarization of the membrane, allowing K⁺ to flow from the cytoplasm to the extracellular fluid down its concentration gradient.

iii.         Ca⁺ channels: of the axon terminal open in response to depolariztion, allowing entry of Ca⁺ from the extracellular fluid into the cell where it serves as a signal to initiate exocytosis of neurotransmitter into the synapse.

iv.         CL^- channels: opened by a variety of neurotransmitters. allowing CL^- to move into the cell down its concentration gradient, hyperpolarizing the cell.

b.         Types of gated Na⁺ channels:

i.            mechanically gated Na⁺ channels are found in sensory neurons and open in response to physical forces such as pressure or light.

ii.            chemically gated Na⁺ channels in neurons respond to a variety of ligands found in the internal and external environments and to neurotransmitters and neuromodulators.

iii.         voltage gated Na⁺ channels play an important role in the conduction of electrical signals along the axon.

c.            Summary:

i.            electrical signaling in neurons results from changes in the cell membrane potential.

ii.          ion channels in the cell membrane open in response to a variety of stimuli.

iii.         when ion channels open, ions move into or out of the cell, their direction of movement depending on the concentration and electrical gradients for the ion.

iv.            Potassium ions usually move out of the cell; Na⁺ , Ca⁺ , CL^- usually flow into the cell.

v.         the net movement of electrical charge across the membrane depolarizes or hyperpolarizes the cell, creating an electrical signal.

10.            Characteristics of Ion-induced membrane potential

a.         A significant change in membrane potential occurs with the movement of very few ions:

i.          for example, to change the membrane potential by 100mV, only one out of every 100,000 K⁺ must enter or leave the cell.

ii.            distribution of charges in nerve fibers exhibit electrical neutrality; that is, for every positive ion, there is a negative ion nearby to neutralize it.

iii.         when positive charges are pumped to the outside of the membrane, these positive charges line up along the outside of the membrane and on the inside the anions that have been left behind line up.

iv.         this creates a dipole layer of positive and negative charges between the inside and outside of the membrane.

v.         hence, to create a negative potential inside the membrane, only enough positive ions must be transported outward to develop the electrical dipole layer at the membrane itself.

vi.         all the remaining ions inside the nerve fiber can still be both positive and negative ions.

b.         The concentration of ions inside and outside the cell remains unchanged essentially as movement of ions across the membrane to generate potentials involve only a minute amount of ions.

12.       There are 2 electrical signals in neurons:

a.         Graded potentials: they are variable-strength signals that lose strength as they travel through the cell.

b.         Action potentials: they can travel for long distances through the neuron without losing strength.

13.            Graded Potentials

a.         Graded potentials are depolarizations or hyperpolarizations of the cell membrane:

i.          they occur mostly in the dendrites and cell body.

ii.          they are called ‘graded’ because the amplitude of a graded potential is directly proportional to the strength of the triggering event.

iii.         a large stimulus will cause a strong graded potential, and a small stimulus will result in a weak graded potential.

iv.         it can either be depolarizing (with opening of Na channels), or hyperpolarizing (with opening of K or CL channels).

b.         Graded potentials begin on the cell membrane at the point where ions enter from the extracellular fluid:

i.          upon binding of a acetylcholine on receptors on the dendrites, Na ion channels are opened.

ii.          the entry of Na ions into the cell causes depolarization of the cell membrane.

iii.         this wave of depolarization is called a local current or electrontonic current.

c.         The strength of the initial depolarization or hyperpolarization in a graded potential is determined by the number of charges that enter the cell, which is in turn determined by the number of receptors which are opened.

d.         Hence the strength of the graded potential is determined by the concentration of the neurotransmitters that bind to the receptors.

e.         The size of the graded potential decreases as it spread out from its point of origin.

f.          Graded potentials travel through the neurons until they reach the trigger zone, the point where an action potential is generated:

i.          in efferent neurons, the trigger zone is at the axon hillock and in the very first part of the axon known as the initial segment.

ii.          in sensory neurons, the trigger zone is immediately adjacent to the receptor, where the dendrites join the axon.

g.         The trigger zone is the integrating center of the neuron:

i.          if graded potentials reaching the trigger zone depolarize the membrane to the threshold voltage, an action potential is initiated.

ii.          if the depolarization does not reach threshold, it simply dies out.

iii.         a depolarization graded potential is called an excitatory postsynaptic potential (EPSP).

iv.         a hyperpolarization graded potential is called an inhibitory postsynaptic potential (IPSP).

14.            Summation of Impulses

a.         Spatial Summation:

i.          if multiple stimuli arrive simultaneously, their graded potentials will be addictive.

ii.          this allows for several subthreshold potential to sum up to a suprathreshold potential large enough to generate an action potential.

iii.         the initiation of an action potential from the addition or summation of several simultaneous subthreshold graded potentials (EPSPs) is spatial summation.

b.            Temporal Summation:

i.          if two subthreshold graded potentials arrive at the trigger zone at almost the same time, the second graded potential adds its depolariztion to that of the first, allowing the trigger zone to depolarize to threshold.

ii.            summation that occurs from graded potentials overlapping in time is called temporal summation.

c.            Summation of graded potentials demonstrates a key property of neurons: postsynaptic integration

i.          when multiple, and sometimes conflicting signals (EPSPs and IPSPs) reach a neuron, postsynaptic integration allows the neuron to evaluate the strength and duration of the signals.

ii.          if the resultant integrated signal is above threshold, the neuron fires an action potential.

15.       Action Potentials

a.         They are rapid electrical signals that pass along the axon to the axon terminal.

b.         Action potentials are identical to each other and they do not diminish in strength as they travel through the cell.

c.         An action potential measured at the distal end of an axon is identical to the action potential that started at the trigger zone.

d.         The strength of the graded potential that initiates an action potential has no influence on the action potential as long as it is above threshold.

e.            Because action potentials either occurs as maximal depolarization or none at all, they are called ‘all-or-none’ phenomenon.

16.            Comparison of Graded Potential and Action Potential