Exam 2 BBB

Communication Within Neurons

  • Membrane Potential: Difference in charge across the membrane.

    • Resting Potential: Neuron at rest is polarized; inside is more negative than outside (-70 mV).

    • Depolarized: Inside is more positive than outside (-70 mV to +40 mV).

    • Action Potential: If depolarization reaches the threshold of excitation (-55 mV), membrane potential briefly reverses (+40 mV) followed by hyperpolarization.

    • Hyperpolarized: Inside is more negative than outside, even more than resting state (-70 mV to -90 mV).

Neuron at Rest

  • Electrochemical Gradient:

    • Na+: Higher concentration outside.

    • K+: Higher concentration inside.

    • Cl-: Higher concentration outside.

    • Organic Anions: Present only on the inside of the neuron.

Forces Influencing Membrane Potential

  • Membrane Potential: Balance of two opposing forces.

    • Force of Diffusion: Molecules move from areas of higher concentration to low concentration.

      • K+ moves outward.

      • Cl- moves inward.

      • Na+ moves inward.

    • Electrostatic Pressure: Oppositely charged particles attract; like charges repel.

      • K+ moves inward.

      • Cl- moves outward.

      • Na+ moves inward.

  • Sodium-Potassium Pump:

    1. Pumps Na+ out of the neuron.

    2. Membrane is not permeable to Na+.

Action Potential Process

  • Initiation: Enough depolarizing stimuli to reach threshold.

  • Voltage-Gated Na+ Channels: Open causing Na+ to rush into the cell.

  • K+ Channels: Open, allowing K+ to exit the cell.

  • Na+ Channels: Close after brief opening.

  • K+ Outflow: Continues until the cell returns to resting state.

  • Hyperpolarization: More K+ exits, temporarily making the cell more negative.

Saltatory Conduction

  • Function: Begins at the trigger zone and conducts along the axon.

  • Characteristics:

    • Action potentials (AP) remain constant in size and amplitude (all-or-none).

    • Intensity changes the rate of firing (rate law).

    • AP travels faster in myelinated axons, retriggered at nodes of Ranvier (contact with extracellular fluid).

Synaptic Transmission

  • Process: Neurons communicate through synapses.

    1. Action potential reaches presynaptic axon terminal buttons.

    2. Voltage change opens voltage-dependent Ca++ channels.

    3. Ca++ flows in (greater concentration outside).

    4. Ca++ binds to proteins on vesicles, causing docking and fusion pore formation.

    5. Presynaptic vesicles release neurotransmitters into the synaptic cleft.

Post-Synaptic Effects of Neurotransmitters

  • Binding: Postsynaptic neurons have binding sites called postsynaptic receptors, fitting specific molecules like puzzle pieces.

  • Effects: Neurotransmitters can have either:

    • Excitatory Effects: Cause depolarization (Na+ enters).

    • Inhibitory Effects: Cause hyperpolarization (K+ exits).

Receptor Types

  • Two General Types of Receptors:

    • Ionotropic Receptors: Contain a binding site for neurotransmitters and an ion channel that opens upon binding.

    • Metabotropic Receptors: Contain a binding site that activates a G protein, producing a second messenger that opens ion channels elsewhere.

Psychopharmacology: Drug Effects on Synaptic Transmission

  • Drugs' Classification:

    • Agonists: Facilitate neurotransmitter effects.

    • Antagonists: Inhibit neurotransmitter effects.

    • Examples of Agonists: Precursors, stimulate NT release, block autoreceptors, inhibit reuptake.

    • Examples of Antagonists: Prevent NT storage, inhibit NT release, block postsynaptic receptors.

Types of Neurotransmitters

  • Excitatory Neurotransmitters: Cause EPSP (excitatory postsynaptic potentials).

    • Examples: Glutamate, Acetylcholine, Adrenaline, Histamine.

  • Inhibitory Neurotransmitters: Cause IPSP (inhibitory postsynaptic potentials).

    • Examples: GABA, Glycine.

  • Major Neurotransmitters: Glutamate and GABA are the two primary neurotransmitters in the brain.

Molecular Structure of Neurotransmitters

  • Amino Acids:

    • Glutamate (EPSP), GABA (IPSP), Glycine (IPSP).

  • Monoamines:

    • Serotonin, Histamine, Dopamine, Epinephrine, Norepinephrine (last three are catecholamines).

  • Peptides:

    • Endorphins (Opioids).

  • Other:

    • Acetylcholine.

Specific Neurotransmitter Functions and Inactivation

  • Glutamate:

    • Principal excitatory NT in brain and spinal cord.

    • Synthesis:

      • Precursor: Glutamine; Enzyme: Glutaminase.

    • Storage: In synaptic vesicles by glutamate transporters.

    • Receptor Binding: NMDA, AMPA, Kinate, Metabotropic Glutamate Receptors.

    • Inactivation: Glutamine synthetase and reuptake.

  • GABA:

    • Principal inhibitory NT in brain and spinal cord.

    • Synthesis:

      • Precursor: Glutamic acid; Enzyme: GAD.

    • Storage: In synaptic vesicles by GABA transporter.

    • Receptor Binding: GABA-A (ionotropic) & GABA-B (metabotropic).

    • Inactivation: GABA transporter or GABA aminotransferase.

  • Acetylcholine (ACh):

    • Primary NT in peripheral and autonomic NS.

    • Synthesis: Precursor: Choline & Acetyl coenzyme A; Enzyme: ChAT.

    • Storage: In synaptic vesicles by ACh transporter.

    • Receptor Binding: Nicotinic (ionotropic) & Muscarinic (metabotropic).

    • Inactivation: Breakdown by acetylcholinesterase.

  • Dopamine:

    • Excitatory & inhibitory roles in movement, attention, learning, and reward systems.

    • Synthesis:

      • Precursor: Tyrosine; Enzyme: Tyrosine hydroxylase.

    • Storage: Vesicular monoamine transporters.

    • Receptor Binding: D1, D2, D3, D4 (all metabotropic).

    • Inactivation: Reuptake by dopamine transporter and breakdown by Monoamine oxidase (MAO).

  • Norepinephrine:

    • Found in CNS & autonomic NS; excitatory & inhibitory.

    • Synthesis: In synaptic vesicles from dopamine; Enzyme: Dopamine β-hydroxylase.

    • Storage: Vesicles in axonal varicosities.

    • Receptor Binding: α and β adrenergic receptors (all metabotropic).

    • Inactivation: Removed by norepinephrine transporter and breakdown by MAO-A.

  • Serotonin (5-HT):

    • Excitatory & inhibitory, influences mood, sleep, eating, pain, arousal.

    • Synthesis:

      • Precursor: Tryptophan; Enzyme: Tryptophan hydroxylase.

    • Storage: In vesicles and released at synaptic terminal.

    • Receptor Binding: At least nine (mostly metabotropic).

    • Inactivation: Removed by serotonin transporter and broken down by MAO.

  • Opioids:

    • Peptides with functions including analgesia and euphoria.

    • Endogenous Opioids: Beta-endorphin, enkephalin, dynorphin.

    • Synthesis: From large polypeptides, breakdown occurs in soma.

    • Storage: Packaged in vesicles, released from all parts of terminal buttons.

    • Receptor Binding: μ (mu), δ (delta), κ (kappa).

    • Inactivation: Not reuptaken, destroyed by enzymes.

Cholinergic Drugs Effects

  • Botulinum: ACh antagonist; prevents release, causes muscle paralysis.

  • Black Widow Spider Venom: ACh agonist; causes muscle contractions.

  • Nicotine and Muscarine: ACh agonists; activate nicotinic and muscarinic receptors, respectively.

  • Curare and Atropine: ACh antagonists; block nicotinic and muscarinic receptors, respectively.

Dopaminergic Drugs Effects

  • AMPT: Dopamine antagonist; blocks activity of tyrosine hydroxylase.

  • Reserpine: Dopamine antagonist; interferes with storage of monoamines in vesicles.

  • Monoamine Oxidase (MAO): Dopamine antagonist; enzyme that destroys monoamines.

  • Amphetamines: Potent dopamine agonists; cause transporters for dopamine and norepinephrine to reverse.

Serotonergic & Noradrenergic Drugs Effects

  • PCPA: Serotonin antagonist; inhibits activity of tryptophan hydroxylase.

  • Fluoxetine: Serotonin agonist; inhibits reuptake of 5-HT.

  • LSD: Direct agonist for serotonin; mimics 5-HT.

  • Moclobemide: Norepinephrine agonist; blocks MAO-A.