Ch12 Nervous System and Action Potentials (PT3)

Introduction to the Nervous System

The nervous system is the central focus of the discussion, serving as the foundation for understanding the concepts of action potentials and subsequent muscle contractions.

Methods of Learning

  • Emphasis on the importance of memorization but encourages understanding through methods that involve thinking through the material.

  • A mention of memorizing muscle names as an essential skill moving ahead into muscle anatomy.

Action Potentials: A Recap

Graded Potentials

  • A graded potential occurs when sodium ions flow in, changing the resting membrane potential of about -70 mV towards a less negative value (e.g., -68, -67).

  • A graded potential must reach a threshold value of -55 mV to trigger an action potential.

  • If this threshold is not reached, the signal will not propagate down the axon as an action potential; it remains a graded potential.

All-or-Nothing Response

  • The action potential follows an all-or-nothing principle: if the threshold of -55 mV is surpassed at the axon hillock, an action potential will occur.

  • This process involves summation of all excitatory and inhibitory inputs at the axon hillock.

Phases of an Action Potential

Depolarization

  • Once the threshold is reached, voltage-gated sodium channels open, allowing a surge of sodium ions into the cell, driving the membrane potential towards +30 mV.

  • This results in a rapid depolarization phase, characterized as the membrane potential shifts towards a more positive charge.

Repolarization

  • Following the peak of depolarization, potassium channels open, allowing potassium ions to exit the cell, which reverses the depolarization, consequently repolarizing the membrane back towards resting potential.

  • Hyperpolarization can occur if too much potassium exits, causing the membrane potential to drop even below the original resting level (potentially to -80 mV).

Refractory Periods

  • Absolute Refractory Period: During this time, no new action potential can be initiated regardless of the stimulus intensity, occurring when sodium channels are open or inactivated.

  • Relative Refractory Period: A new action potential can occur, but a stronger-than-normal stimulus is required due to the hyperpolarized state of the membrane.

Conduction of Action Potentials

Continuous Conduction

  • Happens in unmyelinated axons where action potentials are propagated via sequential opening and closing of sodium and potassium channels along the entire length of the axon. It takes approximately 1 millisecond per segment to propagate, making it relatively slow (15 meters/second).

Saltatory Conduction

  • Occurs in myelinated axons at the Nodes of Ranvier, where the action potential 'jumps' from node to node, significantly increasing conduction speed (up to 150 meters/second).

  • Myelin acts as an insulator, preventing ion leakage and allowing the electrical impulse to propagate much faster through this mechanism.

Factors Influencing Speed of Conduction

  • Myelination: Presence of myelin increases the speed of impulse significantly due to saltatory conduction.

  • Axon Diameter: Larger diameter axons conduct impulses faster, similar to how a wider garden hose can move more water than a narrow one.

Neurotransmitter Release and Action

Arrival at the Synapse

  • When the action potential reaches the axon terminal, calcium channels open, allowing calcium ions to flow into the neuron, promoting the release of neurotransmitters from synaptic vesicles via exocytosis.

Binding and Response

  • Neurotransmitters released into the synaptic cleft bind to receptors on the postsynaptic neuron, which can lead to various physiological responses (either excitatory or inhibitory).

  • Acetylcholine is an important neurotransmitter discussed, and its breakdown by acetylcholinesterase after activation is essential for stopping the signal.

Types of Neurotransmitters

Acetylcholine

  • Functions in neuromuscular junctions and is broken down by acetylcholinesterase.

Biogenic Amines (e.g., Dopamine, Epinephrine, Norepinephrine)

  • These neurotransmitters play roles in mood and emotional responses.

  • Dopamine is associated with reward pathways, while epinephrine (or adrenaline) is linked to the body’s fight-or-flight response.

Amino Acids

  • Various amino acids function as neurotransmitters in the central nervous system.

Neuropeptides

  • These are involved in pain modulation, such as endorphins and substance P, the latter associated with pain signaling.

Neural Circuit Types

Converging Circuits

  • Sensory neurons converge on a single neuron, providing the brain with integrated and comprehensive information of stimuli.

Diverging Circuits

  • A single neuron branches out to multiple neurons, allowing one signal to affect several pathways in the brain.

Reverberating Circuits

  • Feedback loops where output is fed back into the system for adjustments, essential for learned motor skills.

Parallel and Discharge Circuits

  • Inputs are processed simultaneously across multiple components before converging back to a single output.

Conclusion

  • The concepts of action potentials, neurotransmitter functions, and neural circuit types establish a crucial foundation for understanding the nervous system's role in physiology, particularly in relation to muscle function as discussed in future segments.

Introduction to the Nervous System

The nervous system is the central focus of the discussion, serving as the foundation for understanding the intricate concepts of action potentials and subsequent muscle contractions. It is a complex network of nerves and cells that carry messages to and from the brain and spinal cord to various parts of the body, allowing for communication and coordination of bodily functions.

Methods of Learning
  • Emphasis on the importance of memorization, particularly for anatomical structures like muscle names, but strongly encourages a deeper understanding through active learning methods that involve critical thinking and conceptual application rather than rote memorization alone.

  • A mention of memorizing muscle names as an essential foundational skill moving ahead into muscle anatomy, as precise terminology is crucial for effective communication and clinical practice.

Action Potentials: A Recap

Graded Potentials
  • A graded potential is a short-lived, localized change in membrane potential that can be either depolarizing or hyperpolarizing. It occurs when a stimulus causes specific ion channels (ligand-gated or mechanically-gated) to open, allowing a small influx of sodium ions (Na^+) into the cell, thus changing the resting membrane potential of about -70 mV towards a less negative value (e.g., -68 mV, -67 mV). The strength of a graded potential is directly proportional to the strength of the stimulus.

  • To trigger an action potential, a graded potential must reach a critical threshold value, typically around -55 mV, at the axon hillock. This is the
    threshold potential.

  • Graded potentials are decremental, meaning their strength diminishes with distance from the point of origin. If this threshold is not reached, the localized signal will not propagate down the axon as an action potential; it will simply dissipate and remain a subthreshold graded potential.

All-or-Nothing Response
  • The action potential follows an absolute all-or-nothing principle: if the threshold of -55 mV is surpassed at the axon hillock, a full-strength action potential will unfailingly occur and propagate without decrement along the axon. Conversely, if the threshold is not reached, no action potential will fire.

  • This process involves the spatial and temporal summation of all excitatory (depolarizing) and inhibitory (hyperpolarizing) postsynaptic potentials (EPSPs and IPSPs) that arrive at the axon hillock. The net effect determines whether the threshold is met.

Phases of an Action Potential

Chronological Steps of an Action Potential
  1. Resting State:

    • The neuron maintains a resting membrane potential of approximately -70 mV, established by the unequal distribution of ions and the activity of the Na^+/K^+ pumps. Voltage-gated Na^+ and K^+ channels are closed, while K^+ leak channels are open.

  2. Graded Potential (Local Depolarization):

    • A subthreshold stimulus causes a small, localized influx of Na^+ ions, making the membrane slightly less negative (e.g., from -70 mV to -68 mV). This graded potential is decremental and its strength is proportional to the stimulus intensity.

  3. Threshold Stimulus:

    • If the graded potential reaches the axon hillock and depolarizes the membrane to the threshold potential of -55 mV, an action potential will be generated in an all-or-nothing fashion.

  4. Depolarization (Rising Phase):

    • Upon reaching threshold, voltage-gated Na^+ channels rapidly open, leading to a massive influx of Na^+ ions into the cell. This causes a rapid increase in membrane potential, driving it from -55 mV up to a peak of approximately +30 mV.

  5. Repolarization (Falling Phase):

    • At the peak of depolarization (around +30 mV), voltage-gated Na^+ channels inactivate and voltage-gated K^+ channels slowly open. K^+ ions rapidly flow out of the cell, returning the membrane potential to a negative state.

  6. Hyperpolarization (Undershoot):

    • Voltage-gated K^+ channels close slowly, resulting in an excessive efflux of K^+ ions. This causes the membrane potential to briefly drop below the resting potential (e.g., to -80 mV), making it harder for another action potential to fire.

  7. Restoration of Resting Potential:

    • The Na^+/K^+ pump actively transports Na^+ out and K^+ into the cell, restoring the ion gradients and bringing the membrane potential back to its resting state of -70 mV.

Depolarization
  • Once the threshold is reached, voltage-gated sodium channels open, allowing a surge of sodium ions into the cell, driving the membrane potential towards +30 mV.

  • This results in a rapid depolarization phase, characterized as the membrane potential shifts towards a more positive charge.

Repolarization
  • Following the peak of depolarization, potassium channels open, allowing potassium ions to exit the cell, which reverses the depolarization, consequently repolarizing the membrane back towards resting potential.

  • Hyperpolarization can occur if too much potassium exits, causing the membrane potential to drop even below the original resting level (potentially to -80 mV).

Refractory Periods
  • Absolute Refractory Period: During this time, no new action potential can be initiated regardless of the stimulus intensity, occurring when sodium channels are open or inactivated.

  • Relative Refractory Period: A new action potential can occur, but a stronger-than-normal stimulus is required due to the hyperpolarized state of the membrane.

Conduction of Action Potentials

Continuous Conduction
  • Happens in unmyelinated axons where action potentials are propagated via sequential opening and closing of sodium and potassium channels along the entire length of the axon. It takes approximately 1 millisecond per segment to propagate, making it relatively slow (1-15 meters/second).

Saltatory Conduction
  • Occurs in myelinated axons at the Nodes of Ranvier, where the action potential 'jumps' from node to node, significantly increasing conduction speed (up to 150 meters/second).

  • Myelin acts as an insulator, preventing ion leakage and allowing the electrical impulse to propagate much faster through this mechanism.

Factors Influencing Speed of Conduction

  • Myelination: Presence of myelin increases the speed of impulse significantly due to saltatory conduction.

  • Axon Diameter: Larger diameter axons conduct impulses faster, similar to how a wider garden hose can move more water than a narrow one.

Neurotransmitter Release and Action

Chronology of Synaptic Transmission
  1. Action Potential Arrives:

    • An action potential reaches the axon terminal of the presynaptic neuron, depolarizing the presynaptic membrane.

  2. Calcium Channel Opening:

    • The depolarization from the action potential triggers the opening of voltage-gated Ca^{2+} channels located on the presynaptic axon terminal membrane.

  3. Calcium Influx:

    • Extracellular Ca^{2+} ions rapidly flow into the presynaptic terminal, driven by their concentration gradient.

  4. Neurotransmitter Release (Exocytosis):

    • The influx of Ca^{2+} acts as a signal, promoting synaptic vesicles (containing neurotransmitters) to move towards and fuse with the presynaptic membrane. Neurotransmitters are then released into the synaptic cleft.

  5. Diffusion Across Cleft:

    • Released neurotransmitters diffuse across the approximately 20-50 nm wide synaptic cleft to reach the postsynaptic membrane.

  6. Binding to Receptors:

    • Neurotransmitters bind to specific ligand-gated receptor proteins located on the postsynaptic neuron's membrane.

  7. Postsynaptic Potential Generation:

    • This binding causes a conformational change in the receptor, leading to the opening of associated ion channels. This results in either an Excitatory Postsynaptic Potential (EPSP) (depolarization) or an Inhibitory Postsynaptic Potential (IPSP) (hyperpolarization) in the postsynaptic neuron.

  8. Signal Termination:

    • The effect of neurotransmitters is rapidly terminated to allow for precise signaling. This occurs through several mechanisms: enzymatic degradation (e.g., acetylcholinesterase breaking down acetylcholine), reuptake into the presynaptic terminal or glial cells, or diffusion away from the synaptic cleft.

Arrival at the Synapse
  • When the action potential reaches the axon terminal, calcium channels open, allowing calcium ions to flow into the neuron, promoting the release of neurotransmitters from synaptic vesicles via exocytosis.

Binding and Response
  • Neurotransmitters released into the synaptic cleft bind to receptors on the postsynaptic neuron, which can lead to various physiological responses (either excitatory or inhibitory).

  • Acetylcholine is an important neurotransmitter discussed, and its breakdown by acetylcholinesterase after activation is essential for stopping the signal.

Types of Neurotransmitters

Acetylcholine
  • Primary functions: Functions prominently at neuromuscular junctions, facilitating muscle contraction. Also plays roles in the central nervous system, involved in learning, memory, and attention.

  • Termination: Broken down by acetylcholinesterase (AChE) in the synaptic cleft.

Biogenic Amines (e.g., Dopamine, Epinephrine, Norepinephrine)
  • These neurotransmitters are derived from amino acids and include catecholamines and indolamines. They play crucial roles in mood, emotion, reward, and arousal.

  • Dopamine (DA): Associated with reward pathways, pleasure, motor control, and motivation. Imbalances are linked to Parkinson's disease and schizophrenia.

  • Norepinephrine (NE) / Noradrenaline: Involved in alertness, arousal, attention, and the fight-or-flight response. Primarily synthesized from dopamine.

  • Epinephrine (EPI) / Adrenaline: Functions as both a neurotransmitter in the CNS and a hormone released by the adrenal medulla. Plays a key role in the body’s acute stress response (fight-or-flight).

  • Serotonin (5-HT): Influences mood, sleep, appetite, and well-being. Imbalances are often implicated in depression and anxiety disorders.

Amino Acids
  • These are the most common neurotransmitters in the central nervous system, mediating the majority of excitatory and inhibitory synaptic transmission.

  • Glutamate: The primary excitatory neurotransmitter in the CNS, crucial for learning and memory (long-term potentiation).

  • GABA (gamma-aminobutyric acid): The primary inhibitory neurotransmitter in the CNS, reducing neuronal excitability throughout the nervous system.

  • Glycine: An inhibitory neurotransmitter primarily found in the spinal cord and brainstem.

Neuropeptides
  • These are chains of amino acids that function as neurotransmitters, often co-released with other small-molecule neurotransmitters and involved in modulating slower, ongoing brain functions.

  • Substance P: A key neuropeptide associated with pain signaling and inflammation, transmitting pain signals from peripheral sensory neurons to the central nervous system.

  • Endorphins (e.g., enkephalins): Natural opioids that function as pain modulators and create feelings of euphoria, often released during exercise, excitement, or stress.

Neural Circuit Types

Converging Circuits
  • In a converging circuit, multiple presynaptic neurons transmit impulses to a single postsynaptic neuron. This allows for the integration of inputs from various sources onto one neuron, providing the brain with integrated and comprehensive information of stimuli. For example, sensory information from different parts of the body can converge on a single interneuron for processing.

Diverging Circuits
  • A diverging circuit involves a single presynaptic neuron branching out (diverging) to synapse with multiple postsynaptic neurons. This allows one signal to affect several pathways simultaneously in the brain or body. For example, a single motor neuron in the brain can send signals to many muscle fibers, causing widespread contraction.

Reverberating Circuits
  • Reverberating circuits are characterized by feedback loops where the output of a neuron feeds back into the system, either directly or via interneurons, to re-excite the initial sensory neuron or other neurons in the circuit. This mechanism is essential for sustained activity, such as rhythmic breathing, short-term memory, and the consolidation of learned motor skills by allowing the signal to cycle repeatedly.

Parallel After-Discharge Circuits
  • In parallel after-discharge circuits, an input neuron stimulates several neurons arranged in parallel. Each parallel pathway consists of varying numbers of synapses, leading to different conduction delays. All these parallel neurons eventually converge back onto a single output neuron. This arrangement ensures that the input signal is processed simultaneously across multiple components before converging back to a single output, often resulting in a prolonged output signal even after the original input has ceased (after-discharge). This type of circuit can be involved in complex mental functions like mathematical calculations or precise muscle activities requiring sustained input.

Conclusion

  • The detailed understanding of action potentials, the diverse functions of neurotransmitters, and the various neural circuit types establishes a crucial and fundamental foundation for comprehending the nervous system's complex role in overall physiology. This knowledge is particularly vital in relation to muscle function and contraction, a topic that builds directly upon these principles in future anatomical and physiological segments.