Action Potential in Neurons

Stages of an Action Potential

An action potential follows a specific sequence of events. It is an all-or-nothing response, meaning if the neuron reaches a certain voltage threshold, it will fire completely. If not, nothing happens.

1. Depolarization (Threshold Reached at -55mV)

• When a neuron receives a stimulus (e.g., from another neuron), special channels open up.

• If the voltage reaches -55mV, this is called the threshold potential, and an action potential is triggered.

• What happens?

  • Voltage-gated Na⁺ channels open, allowing Na⁺ to rush into the cell.

  • Since Na⁺ is positive, the inside of the neuron quickly becomes less negative.

  • The charge increases from -70mV to around +30mV.

  • At this point, the neuron is depolarized (meaning there is no longer a big difference in charge).

2. Repolarization

• Once the neuron reaches about +30mV, it needs to return to its resting state.

• What happens?

  • Na⁺ channels close, stopping the flow of Na⁺ into the neuron.

  • Voltage-gated K⁺ channels open, allowing K⁺ to exit the neuron.

  • Since K⁺ is positive, its exit makes the inside of the neuron more negative again.

  • The charge starts to drop back toward -70mV.

3. Hyperpolarization (Undershoot Phase)

• K⁺ channels stay open a little too long, allowing too much K⁺ to leave.

• This causes the inside of the neuron to become even more negative than -70mV (around -80mV or lower).

• This is called hyperpolarization, and it temporarily makes it harder for the neuron to fire another action potential.

4. Refractory Period (Reset Phase)

• During this period, the neuron cannot immediately fire again because it needs to reset.

• The sodium-potassium pump helps restore the resting potential by moving Na⁺ back out and K⁺ back in.

• Once the neuron is back at -70mV, it is ready to fire another action potential if needed.

How Action Potentials Travel (Propagation)

Once an action potential starts, it moves down the neuron’s axon toward the next neuron. This process is called propagation.

Unmyelinated Neurons (Slower Conduction)

• In neurons without myelin, the action potential moves continuously down the axon.

• This process is slower because every section of the axon has to go through all the action potential steps.

Myelinated Neurons (Faster Conduction)

• In neurons with a myelin sheath, the action potential "jumps" from one node of Ranvier to the next.

• This is called saltatory conduction, and it makes the signal travel much faster.

Key Takeaways

✔ Resting potential is maintained at -70mV using the sodium-potassium pump and K⁺ leak channels.
✔ Depolarization occurs when Na⁺ enters the neuron, raising the charge inside to +30mV.
✔ Repolarization occurs when K⁺ exits, bringing the voltage back down.
✔ Hyperpolarization temporarily makes the neuron more negative than usual.
✔ The refractory period ensures action potentials move in one direction.
✔ Myelinated neurons conduct signals much faster than unmyelinated ones.

-80 mV: Hyperpolarization Phase (Undershoot)

• After repolarization, the neuron sometimes becomes too negative, dropping below the usual resting potential of -70 mV.

• This can reach around -80 mV (or lower) due to the slow closing of voltage-gated K⁺ channels.

• This makes the neuron temporarily less excitable, meaning it is harder for another action potential to occur.

• The neuron returns to -70 mV as the sodium-potassium pump restores ion balance.

-60 mV: Subthreshold or Near-Threshold Potential

• The neuron's threshold potential (the voltage needed to trigger an action potential) is usually around -55 mV.

• A potential of -60 mV is below threshold, meaning the neuron has been slightly depolarized but not enough to fire an action potential.

• If additional stimulation occurs, bringing the voltage to -55 mV or higher, the action potential will begin.

• If the stimulus is weak and the voltage stays at -60 mV or lower, no action potential occurs.

Summary

• -80 mV: Occurs during hyperpolarization, making it harder for the neuron to fire again immediately.

• -60 mV: A subthreshold potential, meaning the neuron is closer to firing but hasn’t reached the threshold yet.

TTX and TEA in Neuroscience Research

Use of Chemicals in Neuroscience

• Scientists use specific drugs and chemicals to disrupt neuron function in research.

• This helps them study biological processes, including how action potentials work.

Tetrodotoxin (TTX)

• Source: Found in pufferfish.

• Effect: Blocks voltage-gated sodium (Na⁺) channels, preventing action potentials from occurring.

• Use in Research:

  • Shuts down neural and muscular electrical activity.

  • Helps scientists study action potential propagation.

  • Allows researchers to isolate the effects of other signals or drugs.

Tetraethyl Ammonium (TEA)

• Effect: Blocks potassium (K⁺) channels, disrupting the repolarization phase of action potentials.

• Use in Research:

  • Prevents normal neuron recovery after depolarization.

  • Helps study how ion channels contribute to electrical signaling.

Why Scientists Use TTX and TEA

✔ To shut down electrical activity in neurons and muscles.
✔ To analyze how action potentials propagate.
✔ To isolate the effects of other molecules, drugs, or stimuli.

Key Neurotransmitters and Their Functions

1. Acetylcholine

   • Involved in muscle contraction, learning, and memory.

2. Dopamine

   • Plays a role in pleasure, motivation, mood, attention, memory, and movement.

3. Gamma-Aminobutyric Acid (GABA)

   • The primary inhibitory neurotransmitter in the central nervous system.

   • Essential for signal regulation and normal brain function.

4. Glutamate

   • The primary excitatory neurotransmitter in the brain.

   • Found in more than 90% of all brain synapses.

5. Epinephrine and Norepinephrine

   • Excitatory neurotransmitters involved in the fight-or-flight response.

   • Increase arousal and attention.

6. Serotonin

   • Involved in the regulation of mood and sleep.

   • Also helps with digestion.

Neurotransmitters Released in Response to Stress

When encountering a stressful situation, such as encountering a bear in the woods, the following neurotransmitters are likely to be released in higher quantities:

• Glutamate

• Epinephrine

• Norepinephrine

Activity for Understanding Neurotransmitters

Which activity increases serotonin and dopamine levels in the brain the most?

• Answer: Sharing a dessert you enjoy with your friends.

Drug Mechanisms in Neuropharmacology

Researchers study how substances affect neuronal communication by examining their mechanisms of action, which describe how a drug interacts with cells at a molecular level.

Mechanisms of Drug Action

1. Agonist

   • A substance that mimics or enhances the action of a neurotransmitter.

2. Antagonist

   • A substance that blocks or inhibits the action of a neurotransmitter.

3. Inverse Agonist

   • A substance that binds to the receptor but produces the opposite effect of an agonist.

4. Reuptake Inhibitor

   • A substance that prevents the reabsorption of neurotransmitters, leading to their increased availability in the synapse.

Drugs and Their Mechanisms of Action

. Diphenhydramine (Benadryl)

• Mechanism of Action: Antagonist

  • How it works: Diphenhydramine is an antagonist to histamine receptors (specifically H1 receptors). By blocking these receptors, it reduces allergic symptoms like sneezing and itching, but it can also cause sedation because it inhibits histamine’s normal role in maintaining alertness.

2. Morphine

• Mechanism of Action: Agonist

  • How it works: Morphine is an agonist at opioid receptors. It mimics the action of natural pain-relieving neurotransmitters like endorphins, resulting in pain relief and a feeling of euphoria. It binds to opioid receptors in the brain and spinal cord, blocking pain signals.

3. Caffeine

• Mechanism of Action: Antagonist

  • How it works: Caffeine is an antagonist at adenosine receptors. Normally, adenosine promotes relaxation and sleep, but caffeine blocks these receptors, increasing alertness and reducing the feeling of tiredness.

4. Cocaine

• Mechanism of Action: Reuptake Inhibitor

  • How it works: Cocaine acts as a reuptake inhibitor for dopamine, serotonin, and norepinephrine. It prevents these neurotransmitters from being reabsorbed back into the neurons, resulting in an increased presence of these chemicals in the synaptic gap, which leads to intense feelings of euphoria, increased energy, and enhanced mood.

Reward Pathway and Addiction:

The reward pathway, also known as the addiction pathway, is a system of signals in the brain that controls motivated behavior and feelings of pleasure or euphoria. When activated, this pathway gives rise to the feeling of reward, making us feel good and motivating certain behaviors. While this pathway is naturally triggered by pleasurable experiences (like eating or social interactions), it can also be hijacked by drugs like amphetamines, cocaine, and opioids, which overstimulate the system.

Key Components of the Reward Pathway:

• Dopamine:
  The main neurotransmitter involved in the reward pathway is dopamine, which is responsible for the sensation of pleasure and reward. When dopamine is released in the brain, it signals feelings of euphoria or a "high." This release of dopamine is a key element in the addiction process.

• Mu Opioid Receptors:
  Opioids (such as morphine) are substances commonly used to treat pain, but they can also lead to addiction. Opioids interact with mu opioid receptors in the brain, which are found in the midbrain, a critical area of the brain involved in pleasure and reward. When opioids bind to these receptors, they trigger the release of a large amount of dopamine, which then activates the dopamine receptors on the next neuron in the reward pathway.

• Neurotransmission Process:

  • When opioids activate mu opioid receptors, they cause a massive release of dopamine.

  • This release of dopamine then stimulates the dopamine receptors on the next neuron, resulting in a feeling of euphoria or the "high" associated with drug use.

Impact of Repeated Drug Use:

• Limbic System and Memory:

  • The brain’s limbic system (which includes the amygdala and hippocampus) is involved in emotional processing and memory. When the brain experiences the euphoria associated with opioid use, the limbic system stores the pleasurable memory, making the individual more likely to repeat the drug use in the future.

• Tolerance Development:

  • As drug use continues, the brain becomes overstimulated by the euphoria caused by the release of dopamine. In response, the brain adjusts by reducing the number of dopamine receptors in the neurons involved in the reward pathway.

  • This reduction in dopamine receptors means that over time, the same amount of drug produces less of a pleasurable effect.

  • This is the development of drug tolerance, where the user needs to consume higher amounts of the substance to achieve the same feeling of pleasure or euphoria.

Key Brain Areas Involved:

• Midbrain: The area where opioid receptors are located, crucial for reward and pleasure.

• Amygdala: Involved in emotional processing, it helps the brain associate drug use with pleasure.

• Hippocampus: Responsible for forming memories, it stores memories of the pleasurable effects, encouraging repeated drug use.

• Prefrontal Cortex: Involved in decision-making, it plays a role in controlling behavior but can become impaired in addiction, reducing the ability to control drug use.

Summary of the Addiction Process:

1. Initial Drug Use: Drugs like opioids trigger a massive release of dopamine, creating feelings of euphoria or a "high."

2. Memory Formation: The limbic system stores these pleasurable feelings, leading to cravings and a desire to use the drug again.

3. Tolerance Development: The brain adjusts by reducing dopamine receptors, leading to the need for higher doses to achieve the same pleasurable effect.

4. Addiction: Over time, the cycle of use, euphoria, and tolerance can lead to substance use disorder or addiction, where the person is unable to control their drug use despite negative consequences.

By understanding the reward pathway and how opioid receptors work, researchers can better understand the mechanisms of addiction and the challenges in treating it.

• The chemical name: describes the exact chemical composition of the medicine.

• The generic name: more commonly used name of the medication.

• The proprietary or brand name: name assigned by a manufacturer and protected by copyright.

Dosage

• The dose of the drug is the amount a patient takes for a desired effect.

• Some doses are general and not patient specific, but many doses are calculated using specific data about the patient.

• Many factors contribute to determining the

proper dose of a medication, including:

– Route of administration of the medication

– Weight of the patient

– Overall severity of the condition

Routes of Drug Administration

Parenteral Routes (Routes via injection)

• Intravenous Injection (IV)

  • Injections given directly into the veins.

Other Routes of Administration

• Transdermal

  • Administration via skin preparations.

  • Examples: Creams, ointments, lotions, sprays, patches.

• Ophthalmic

  • Medications administered to the eye.

• Otic

  • Medications administered in the ears.

• Nasal

  • Medications administered in the nose.

• Inhalation

  • Administration by drawing breath, gas, or vapor into the lungs.

  • Could be delivered by aerosols, nebulizers, or inhalers.

• Vaginal

  • Administration into the vagina.

• Rectal

  • Administration into the rectum.

Side Effects

• Side effects are the results of drug (or other) therapy that are beyond the desired therapeutic effects.

• Side effects may vary for each individual depending on the person’s disease state, age, weight, gender, ethnicity, or general health.

• Medications undergo rigorous testing before they are released to the public, and all confirmed potential side effects are reported on the literature that comes with a medication.

Drug Interactions

• A drug interaction occurs when the effects of one drug are altered by the effects of another drug.

• The interaction leads to an increase or decrease in effectiveness of the new medication.

• Severe drug interactions can lead to serious consequences in the body, even death.

Anatomy of a Prescription

Example Prescription Might Include:

• Information about the Healthcare Provider

• Patient Information and Date of Prescription

• The RX Symbol

• The Names and Quantity of Ingredients

• Directions for How the Pharmacist is to Fill the Prescription

• Directions for the Patient as to How/When to Take the Medication

• Information about Refills and Special Labeling

Abbreviations Used in Pharmacology

• Doctors use a series of abbreviations to communicate with the pharmacist.

• These abbreviations note:

  • How often to take the medication (twice a day, every 4 hours)

  • When to take the medication (at night, before meals)

  • How much medication to take (one tablet, 100 mg)

  • How to use the medication (apply it topically, take it by mouth)