Neurons: Pumps and Ion Channels

• Neurons form the nervous system's basic functional structure.
• Neurons are excitable cells.
• Electrical signals are initiated and transmitted by neurons.
• Neurons conduct electrical signals throughout the body.
• Neurons can conduct electrical signals due to their ultrastructure of proteins in the plasma membrane.
• Pumps and channels are included in the ultrastructure of proteins.
• The membrane has relative protein concentration.

Pumps

• Pumps are membrane proteins that actively transport ions across the membrane against their concentration gradient.
• Pumps require energy in the form of ATP, making their transport an active process.
• The Na+/K+-ATPase pump serves as a classic example.

Ion Channels

• Ion channels are membrane proteins that enable ions to traverse the membrane.
• H₂O soluble ions must pass through channels to penetrate the plasma membrane.
• Ion channels are selective to allow only a specific ion to pass through.
• Passive mechanisms are employed by ion channels.
• No energy is required for ions to pass through.
• There are two types of ion channels: gated and leak channels.

Gated Channels

• Gated channels can either be opened or closed.
• A change in protein conformation dictates whether the gated channel is open or closed.

Leak Channels

• Leak channels are channels that are open all the time.
• These channels allow for unregulated leakage of their chosen ion across the membrane.

Types of Gated Channels

• Voltage-gated channels respond to changes in membrane potentials.
• Ligand-gated channels respond to a chemical messenger with a closely associated receptor
• Ligand-gated channels may respond to intracellular or extracellular ligands
• Mechanosensitive-gated channels respond to stretching or other mechanical deformation.
• Thermally-gated channels respond to local changes in temperature.

Voltage-Gated Na+ Channels

• There are two gates: activation gate and an inactivation gate.
• Both gates must be open to allow Na+ flow into the cells.
• There are 3 configurations of the channel: closed but capable of opening, open(activated), and closed but incapable of opening(inactivated).

Voltage-Gated Ion Channels

• Most voltage-gated channels have one gate.
• There are two states: open and closed.
• An example is a voltage-gated K+ channel.

Channel & Pump Distribution

• Plasma membrane over the entire neuron, Na+/K+-ATPase, Na+ leak channels, and K+ leak channels are everywhere.
• Pumps and channels are also localized:
  • Receptive segment (dendrites and cell body):
    • Chemically-gated cation(Na+ & K+) channels
    • Chemically-gated K+ channels
    • Chemically-gated Cl- channels
  • Initial segment (Axon hillock)
    • Voltage-gated Na+ channels
    • Voltage-gated K+ channels
  • Conductive segment (axon)
    • Voltage-gated Na+ channels
    • Voltage-gated K+ channels
  • Transmissive segment (axon terminal)
    • Voltage-gated Ca2+ channels
    • Ca2+ pumps.

Ion Movement

• Ion movement is affected by two factors: chemical gradient and electrical gradient.
• Chemical gradient is the difference in the number of ions between two areas.
• Ions passively diffuse from the area of higher concentration to an area of lower concentration.
• Electrical gradient is the difference in charge between two areas.
• The difference in charge can be in the number of charges (e.g. differences in the number of cations) or the differences in the number of opposite charges.
• Ions move towards an area of opposite charge.
• Both factors at work constitute the electrochemical gradient.
• Generally, electrical and chemical gradients oppose one another.

Membrane Potential

• Keeping charges separate requires energy input accomplished by the plasma membrane.
• The difference in charges across a plasma membrane is called a membrane potential.
• It is a form of potential energy.
• The membrane itself carries no charge, and the difference in charge is in the localized fluid on either side of the plasma membrane.
• All cells have membrane potentials.
• Excitable tissues (muscles, nerves) can produce rapid, transient changes in their membrane potential, which serve as electrical signals.

Measuring Membrane Potentials

• A voltmeter measures the difference in charge (voltage) across the plasma membrane.
• The electrode outside the cell serves as the reference.
• The electrode inserted into the cell serves as a record.
• The voltmeter reports the charge inside the cell relative to the outside.
• A negative value means the inside of the cell has a negative charge relative to the outside.
• A positive value indicates the inside of the cell has a positive charge relative to the outside.
• Membrane potentials are measured in mV.
• It is a measure of the cell's ability to do work.

Factors Responsible for Membrane Potentials

• Plasma membrane's permeability to ions.
• The permeability of ions is dependent on the types and number of pumps and channels found within the membrane and their localization.
• Unequal distribution of key ions in the ICF and ECF and their selective movement between these two areas.
• Na+, K+, and anionic cellular proteins (A-) are largely responsible for resting membrane potential.

Ions and Membrane Potential

• Na+/K+-ATPase is responsible for moving K+ into the cell and moving Na⁺ out of the cell.
• Na+/K+-ATPase leads to steep concentration gradients for each ion.
• K+ has lots of leak channels.
• Steep gradients favor the movement out of the cell.
• Movement stops when the concentration gradient (out) equals the electrical gradient (in).
• The membrane is impermeable to A-.
• A- serves to attract cations into the cell.
• A- establishes a negative charge inside of the cell as K+ leaves down its concentration gradient.
• Na+ has very few leak channels.
• Steep gradient favors the movement into the cell.
• Movement stops when the concentration gradient (in) equals the electrical gradient (out).
• Cl- serves to attract cations out of the cell.

Effects of K+ and Na+ on Membrane Resting Potential

• 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 towards the ion's own equilibrium potential.
• Increasing permeability for an ion moves membrane potential toward that ion's equilibrium potential.
• Decreasing permeability for an ion moves membrane potential away from that ion's equilibrium potential.
• The membrane of cells is significantly more permeable to K+ than Na+.

Na+ & K+ Leakage

• The -70 mV potential is insufficient to counterbalance the concentration gradient of K+ (-90 mV).
• K+ still leaks out of the cell via K+ leak channels, and there are lots of leak channels.
• The -70 mV potential favors the passive influx of Na+ down its concentration gradient (+60 mV).
• Na+ still leaks into the cell via Na+ leak channels, and there are very few leak channels.
• The Na+/K+ pump actively returns the Na+ & K+ ions back to their respective sides.
• This offsets the leaking and maintains the -70 mV potential.

Membrane Electrical States

• Polarized state is when the membrane potential is other than 0 mV.
• Depolarization is when the membrane becomes less polarized than at resting potential.
• It is a reduction in magnitude.
• Hyperpolarization is when the membrane becomes more polarized than at resting potential.
• It is an increase in magnitude.
• Repolarization is when the membrane returns back to resting potential after having been depolarized or hyperpolarized.
• Electrical signals are produced by changes in ion movement across the plasma membrane.
• Net inward flow of positive ions results in depolarization.
• Net outward flow of positive ions results in hyperpolarization.

Electrical Signals

• Changes in membrane permeability of an ion or alterations of the ion concentration on the two sides of the membrane produce electrical signals.
• There are two kinds of potential changes: graded potentials and action potentials.

Graded Potentials

• Are a local change in potential and occur with varying degrees of magnitude.
• Example, change from -70 mV to -60 mV.
• Example, change form -70 mV to -75 mV.
• Can be either depolarizations or hyperpolarizations.
• Are usually produced by a specific triggering event that causes chemically-gated ion channels to open in a specialized region.
• Are formed by the receptive segment of an excitable cell membrane.
• Result in either Na+ channels being opened.
• Result in depolarization that is confined to a small region of the plasma membrane.
• The magnitude and duration of a graded potential is directly related to the magnitude and duration of the triggering event.
• The stronger the triggering event the more gated channels open, the more ions pass through, the greater the depolarization
• The longer the duration of the triggering event, the longer the duration of the graded potential.
• Decrement in intensity with distance traveled.
• Localized stimulations, the remainder of the membrane remains at resting potential.
• The temporarily depolarized region is the active area.
• Electrical charges move passively from the active area into adjacent area due to the difference in potential.
• Results in a loss in intensity due to resistance to current.
• Graded potentials are short-lived.
• Last only as long as the channels are open and until local current ceases.

Action Potential

• Action potential is generated at the initial segment and propagated along the conductive segment to the transmissive segment.
• Action potential consists of brief, rapid, large changes in membrane potentials.
• The changes can be 100 mV in neurons during which the potential actually reverses.
• Involves only a small portion of the membrane.
• Travels at a non-decremental fashion and do not diminish in strength from the site of initiation as they travel.
• Triggered by the opening of voltage-gated channels in response to changes in membrane potential.
• Must reach a threshold to cause gates to open.
• Obeys the "All or None" law with either the membrane responding to a triggering event with a maximal response or not responding at all.

Post-Synaptic Response

• Presynaptic neurons release neurotransmitters that diffuse across the synaptic cleft and bind to receptors on the post-synaptic neuron.
• Receptors mediate graded responses in the post-synaptic neuron dependent on the amount of NT that is released.
• There are two types of synapses.
  • Excitatory.
  • Inhibitory.

Excitatory Post-Synaptic Potential (EPSP)

• Neurotransmitter is released at the pre-synaptic terminal.
• Binds to receptors which opens chemically-gated cation channels.
• More Na+ moves into the cells than K+ moves out of the cells dependent on the electrochemical gradient.
• A small depolarization in the post-synaptic neuron results.
• The activation of one synapse is usually insufficient to cause depolarization to threshold but brings potential closer to threshold.
• Local current of Na+ diminishes as it progresses towards the axon hillock.

Inhibitory Post-Synaptic Potential (IPSP)

• Neurotransmitter released at the pre-synaptic terminal binds to receptors which opens channels for either K+ or Cl-
• Either Cl- moves into the cells or K+ moves out of the cells dependent on the electrochemical gradient.
• A small hyperpolarization in the post-synaptic neuron results.
• The activation of one synapse is usually insufficient to cause depolarization to threshold but brings potential further from threshold.
• Local current of K+ or Cl- diminishes as it progresses towards the axon hillock.

Role of EPSPs & IPSPs

• The end result of an EPSP is a local graded potential bringing the membrane potential closer to threshold.
• The function of the EPSP is to help trigger an action potential at the axon hillock.
• The end result of an IPSP is that the membrane potential is driven further from threshold.
• The response at the post-synaptic neuron is a composite of all the EPSPs and IPSPs at the same time.
• The total potential is called the grand postsynaptic potential (GPSP.
• For the post-synaptic neuron to fire (produce an action potential), it must reach threshold.
• This is achieved through Temporal summation and Spatial summation.

Summation

• Spatial Summation: Simultaneous firing of more than one action potential from different presynaptic inputs to reach threshold.
• Temporal Summation: Successive firing of a single presynaptic neuron.
• Cancellation: Simultaneous activation of an EPSP and an IPSP so that the sum of magnitudes cancels each other out.