Nervous System Overview

• The nervous system relies on neurons to stimulate muscles and glands, facilitating communication.

Neuron Structure and Function

• Dendrites serve as the input area, receiving signals from other neurons.
• The soma (cell body) acts as the input area and is the primary nutritional and metabolic center for the neuron.
• The axon functions as the conductive region, generating action potentials.
• Signals from other neurons are received at synapses, primarily located on dendrites and soma, these are the neuron's receptive regions.
• The axon hillock is where the axon emerges from the soma and where the outgoing signal (action potential) is generated.
• Axons can branch to form axon collaterals, and they terminate in many axon terminals.
• Neurons typically have one long axon and many branched dendrites.
• Most central nervous system neurons are multipolar.
• Ion channels in the cell membrane are formed by integral proteins.

Ion Channel Specificity

• Ion channels are selective for specific ions based on their charge and size.

Types of Ion Channels

• Ion channels include leakage, chemically (ligand)-gated, voltage-gated, and mechanically-gated channels.
• A sodium channel that is always open is a leakage channel.
• Sodium ions move into or out of a neuron through leakage channels, depending on the concentration gradient.
• Voltage-gated potassium channels open at +30mV.
• Acetylcholine (ACh) and GABA are neurotransmitters that open chemically gated channels.
  • Activation of ACh channels allows sodium (Na+) ions to pass into the cell.
  • Activation of GABA channels allows chloride (Cl-) ions to pass into the cell.

Ion Channel Location and Potential

• Passive channels are located on dendrites, soma, and axons, leading to resting membrane potential.
• Chemically gated channels are on dendrites and soma, leading to graded potential.
• Voltage-gated channels are on the axon (hillock and onward), leading to the action potential.
• Voltage-gated sodium channels are found along the axon and are important for action potential generation; they open and close by gates.
• A chemically-gated GABA neuroreceptor is a channel through which chloride ions can pass into the cell.
• Tetrodotoxin, a toxin found in Japanese puffer fish, blocks voltage-gated sodium channels & prevents action potentials, leading to muscle paralysis.

Intracellular and Extracellular Ion Concentrations

• Intracellular sodium (Na+) concentration is low, while extracellular concentration is high.
• Intracellular potassium (K+) concentration is high, while extracellular concentration is low.
• Intracellular chloride (Cl-) concentration is non-specific, while extracellular concentration is high.

Membrane Permeability and Ion Movement

• At rest, neurons are more permeable to K+ than to Na+ due to leak channels.
• Alterations affecting membrane permeability to K+:
  • An increase in passive K+ channels increases permeability.
  • Opening of voltage-gated K+ channels increases permeability.
  • Closing of voltage-gated K+ channels decreases permeability.
• The concentration gradient is the chemical force that pushes K+ out of the cell.
• The electrical gradient tends to pull K+ back into the cell.
• The equilibrium potential for K+ is around -90 mV when the two forces are equal and opposite.
• In excitable cells permeable to Na+ and Cl–, the gradients would move Na+ into the cell.
• Gradients oppose the movement of Cl– into the cell.
• The resting membrane potential is -70 mV due to the neuron's permeability to Na+ and K+.
• The sodium-potassium pump compensates for the movement of Na+ and K+ ions.
• Increased extracellular fluid concentration of K+ makes the membrane potential negative.
• Decreased extracellular fluid concentration of K+ makes the membrane potential positive.
• Increased extracellular fluid concentration of Na+ makes the membrane potential negative.
• Decreased number of passive Na+ channels makes the membrane potential negative.
• Opening of voltage-gated K+ channels makes the membrane potential negative.
• Opening of voltage-gated Na+ channels makes the membrane potential positive.

Action Potential Details

• The action potential changes the membrane potential from -70 mV (resting) to +30 mV and back to the resting membrane potential, arising from the opening of voltage-gated ion channels.
• Voltage-gated Na+ channels are most dense at the axon hillock.
• Opening voltage-gated channels at the axon hillock causes the membrane to depolarize.
• If the membrane reaches the threshold, an action potential will be generated.
• During the depolarization phase, voltage-gated K+ channels open and K+ exits the cell triggering repolarization.
• Voltage-gated Na+ channels becoming inactive and voltage-gated K+ channels opening stops the potential from rising above +30 mV.
• The opening of voltage-gated K+ channels causes the membrane to repolarize, with K+ moving out of the cell during repolarization.
• Hyperpolarization occurs if the membrane potential becomes more negative than -70 mV, this is due to the K+ channels being slow to close.
• After an action potential, the neuron cannot generate another action potential due to inactive Na+ channels, known as the absolute refractory period.
• During the relative refractory period, the cell can generate another action potential if the membrane is more depolarized.
• Conduction velocity is increased by the thickness of the axon and myelination.
• Conduction along a myelinated axon is called saltatory conduction.
• Multiple sclerosis is an autoimmune disease that attacks myelin sheaths, causing muscle weakness.

The Synapse Revisited

• Neurons communicate with other neurons stimulate muscles and glands.
• Neurons can either excite or inhibit other neurons.
  • Exciting another neuron increases the chance of an action potential.
  • Inhibiting another neuron decreases the chance of an action potential.
• Synapses between axons of one neuron and dendrites or soma of another are called axodendritic and axosomatic. They carry input signals to the other neuron.
• Axons from one neuron can synapse with the axon terminal of another neuron. These synapses are called axoaxonal and they regulate the amount of neurotransmitter released by the other neuron.
• Electrical synapse: Electrical current flows from one neuron to another through connexons and always results in continuous signal conduction.
• Chemical synapses: A neurotransmitter is released from the sending neuron, travels across the synapse, and binds to the receiving neuron and can be either excitatory or inhibitory.
• Chemical synapses are slower than electrical synapses but are the most common type.
• Presynaptic neuron: The neuron conducting the impulse toward the synapse.
• Axon terminal: Contains vesicles filled with neurotransmitters.
• An action potential in the axon terminal of the presynaptic neuron causes the neurotransmitter vesicle to be released.
• Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane and open ligand gated channels and this movement of charged particles produces a synaptic potential.

Neurotransmitters and Ion Channels - Continued

• Neurotransmitters that bind to ion channels are directly acting neurotransmitters.
  • These directly acting neurotransmitters include Acetylcholine, GABA, Glutamate, and Dopamine.
• Binding of ACh opens ion channels in the dendrites or cell body that permits both Na+ and K+ to move through them.
  • More Na+ moves into the cell and K+ moves out of the cell.
  • This results in depolarization, called an excitatory postsynaptic potential (EPSP).
• An inhibitory postsynaptic potential (IPSP) causes a neuron to hyperpolarize, for example, caused by GABA.
  • In response to GABA, Chloride ions move into the cell.
• Norepinephrine is an indirectly acting neurotransmitter that binds to a receptor separate from the ion channel.
  • Norepinephrine acts as the first messenger.
  • The receptor is coupled to the ion channel by a G protein.

Synaptic Transmission Details

• Action potential causes voltage gated Ca2+ (calcium) channels to open up in the presynaptic neuron, due to the presence of Calcium.
• Neurotransmitters are stored in synaptic vesicles and diffuse across the synaptic cleft and bind to receptors on the postsynaptic neurons.
• Chemically gated ion channels open in response to the neurotransmitters.
• Neurotransmitters are removed from the synaptic cleft via degradation or reuptake.
  • Degradation: Enzymes break down the neurotransmitter, rendering it inactive, for example, Acetylcholinesterase (AChE) breaking down acetylcholine (ACh).
  • Reuptake: Enzymes associated with the postsynaptic membrane or present in the synaptic cleft recycle and reuse the neurotransmitter (as with the neurotransmitter norepinephrine).
• The response on the postsynaptic cell depends on the amount of neurotransmitter released and how long it remains in the area.
  • Synaptic potentials are also known as graded or action potentials.
  • Graded potentials decay as they travel away from the synapse.
• Accumulation of action potentials on an axon causes temporal summation.
• Increasing the number of synapses from different neurons causes spatial summation.
• The most common excitatory neurotransmitter in the CNS is glutamate.
• Two major inhibitory neurotransmitters in the CNS are GABA and Glycine.