Nervous Tissue & System Part 2 Neuronal Membrane Potentials, Action Potentials, and Synaptic Transmission

Membrane Potential States and Phase Mechanics

• Polarization (Resting State):

  • Resting membrane potential maintains an asymmetrical ion distribution where the intracellular environment is negative relative to the extracellular environment.

  • The exact resting membrane potential value to memorize is $-70\,mV$.

• Depolarization:

  • Occurs when an incoming stimulus disrupts the resting state, making the inside of the cell progressively more positive.

  • Voltage-gated sodium ($Na^+$) channels open, driving an influx of positive $Na^+$ ions into the cell.

  • The electrical signal propagates sequentially along the axon toward the terminal end.

• Repolarization:

  • The process of restoring the negative intracellular potential back toward the resting state ($-70\,mV$).

  • Sequence of required physiological steps for repolarization:

  • Closure of Sodium Channels: Voltage-gated $Na^+$ channels close to halt the inward flow of positive ions.

  • Opening of Potassium Channels: Voltage-gated potassium ($K^+$) channels begin opening and eventually open fully.

  • Efflux of Potassium: Because $K^+$ concentration is higher inside the cell, $K^+$ rushes out through the open gated channels down its concentration gradient.

  • Passive Channel Activity: Leaky passive channels remain continuously open throughout the process.

  • Sodium-Potassium Pump Activity: The sodium-potassium ATPase pump ($Na^+/K^+$ ATPase pump) restores ionic homeostasis by actively transporting $3\,Na^+$ ions out of the cell for every $2\,K^+$ ions brought back in.

• Hyperpolarization:

  • Defined as excessive negativity within the cell relative to baseline resting state.

  • Etiology: Voltage-gated $K^+$ channels remain open too long during repolarization, expelling excessive $K^+$ out of the cell.

  • Intracellular charge drops lower than resting state, reaching values such as $-75\,mV$, $-80\,mV$, or $-85\,mV$.

  • Resolution: Gated $K^+$ channels close, and the $Na^+/K^+$ ATPase pump restores membrane potential back to $-70\,mV$ by transporting $2\,K^+$ ions in for every $3\,Na^+$ ions pumped out.

• Refractory Period:

  • A brief recovery window immediately following continuous electrical impulse firing.

  • Axonal ion channels are refractory/occupied and resetting their baseline states.

  • The axon cannot respond to additional incoming impulses, preventing action potential generation during this window.

• Graphing Membrane Potential Dynamics:

  • X-axis: Time measured in milliseconds ($ms$).

  • Y-axis: Membrane potential (distribution of positive and negative charges across the cell membrane) measured in millivolts ($mV$).

Action Potential Generation and Synaptic Transmission Mechanics

• Threshold Potential and Action Potential Firing:

  • Resting Potential: $-70\,mV$.

  • Threshold Potential: $-55\,mV$.

  • Mechanism: A stimulus must open a sufficient number of gated $Na^+$ channels to depolarize the membrane potential from $-70\,mV$ up to $-55\,mV$.

  • Reaching the $-55\,mV$ threshold triggers widespread opening of remaining voltage-gated $Na^+$ channels along the axon, ensuring signal propagation to the terminal end.

  • Peak depolarization reaches positive millivolt values, such as $+30\,mV$, $+45\,mV$, or $+50\,mV$.

  • Synonymous terms for this electrical transmission include: nerve impulse, electrical impulse, and action potential.

• Synaptic Terminal End Structure:

  • The expanded distal end of an axon is termed the terminal bouton or synaptic end bulb.

  • Contains terminal synaptic vesicles, which are membrane-bound containers storing synthesized neurotransmitters.

• Calcium-Mediated Neurotransmitter Release:

  • Step 1: The nerve impulse reaches the terminal bouton.

  • Step 2: Axonal depolarization opens membrane-bound, voltage-gated calcium ($Ca^{2+}$) channels (purple proteins).

  • Step 3: Because $Ca^{2+}$ concentration is higher outside the cell, $Ca^{2+}$ rushes into the terminal bouton through the open gated channels.

  • Step 4: Intracellular $Ca^{2+}$ influx triggers synaptic vesicles to dock and fuse with the terminal membrane.

  • Step 5: Neurotransmitters are released into the synaptic cleft via exocytosis.

  • Step 6: Released neurotransmitter molecules bind to target receptors on:

  • Adjacent Neurons: Facilitating inter-neuronal communication.

  • Muscle Cells: Binding to muscle receptors to initiate contraction cascades.

  • Gland Cells: Binding to glandular receptors to mediate specific physiological responses.

Graded vs. Action Potentials and Axonal Conduction Velocity

• Graded Potentials:

  • Characterized by depolarization strength that diminishes or slows down over time and distance as it travels along the axon.

  • Effective for short-distance cellular communication.

  • Example: Bipolar neurons in the retina receive inputs from photoreceptors and transmit signals across short distances to cranial nerve neurons bound for the brain.

• Action Potentials:

  • Operates via an "all-or-none" mechanism requiring the membrane potential to hit threshold ($-55\,mV$).

  • Maintains signal strength across long distances without diminishing (e.g., transmission from a fingertip to the spinal cord and brain).

• Conduction Velocity Factors:

  • Speed of electrical impulse transmission along an axon depends on myelination.

• Continuous Conduction:

  • Occurs in unmyelinated axons.

  • Voltage-gated channels open sequentially along every adjacent segment of the axon.

  • Propagation is relatively slow (minimal distance covered across $1\,ms$, $5\,ms$, and $10\,ms$ intervals).

  • Utilized by slow pain nerve fibers.

• Saltatory Conduction:

  • Occurs exclusively in myelinated axons.

  • Active voltage-gated channels and active impulse generation are restricted to unmyelinated gaps called Nodes of Ranvier.

  • Myelinated segments conduct electrical signals passively.

  • Displays a rapid skipping pattern ("pop, skip, pop, skip") as the signal passively traverses myelin and actively regenerates at Nodes of Ranvier.

  • Achieves fast conduction velocity (covers significant distance within $10\,ms$).

  • Utilized by fast pain / sharp pain nerve fibers.

Neurotransmitter Receptors and Postsynaptic Potentials (EPSP and IPSP)

• Ionotropic Receptors (Ion Channel Receptors):

  • Receptor proteins that function directly as ion channels.

  • Mechanism: Direct binding of a neurotransmitter opens or closes the channel, producing a rapid cellular response.

  • Example: Acetylcholine ($ACh$) binding to ionotropic receptors on skeletal muscle cells opens $Na^+$ channels, causing $Na^+$ entry, membrane depolarization, and muscle contraction.

• Metabotropic Receptors (G-Protein Coupled Receptors - GPCRs):

  • Receptor proteins that are distinct from ion channels, resulting in slower cellular responses due to multi-step cascades.

  • Signaling Cascade:

  1. Ligand (e.g., epinephrine) binds to the metabotropic receptor.

  2. G-protein complex subunits dissociate.

  3. Activated G-protein subunit stimulates an intracellular enzyme.

  4. The enzyme converts adenosine triphosphate ($ATP$) into cyclic adenosine monophosphate (cAMP).

  5. cAMP activates protein kinases.

  6. Kinases phosphorylate targets to open or close ion channels or alter cellular activity.

• Synapse Definitions:

  • Synapse: The functional junction where a presynaptic neuron releases neurotransmitters to communicate with a postsynaptic cell (neuron, muscle, or gland).

  • Postsynaptic Potential: The local electrical change induced in the postsynaptic cell membrane following neurotransmitter binding.

• Excitatory Postsynaptic Potential (EPSP):

  • Produces a depolarizing/stimulatory response, shifting membrane potential toward threshold.

  • Mechanism: Release of glutamate into the synapse -> glutamate binds to receptors -> opens $Na^+$ channels -> positive $Na^+$ influx -> depolarization -> reaches $-55\,mV$ threshold -> excitatory action potential.

• Inhibitory Postsynaptic Potential (IPSP):

  • Produces a hyperpolarizing/inhibitory response, shifting membrane potential further away from threshold.

  • Mechanism: Release of GABA into the synapse -> GABA binds to receptors -> opens chloride ($Cl^-$) channels -> $Cl^-$ influx (higher $Cl^-$ concentration outside cell) -> intracellular environment becomes more negative than $-70\,mV$ -> hyperpolarization -> suppression of impulse firing.

Synaptic Integration and Summation Mechanisms

• Concept of Summation:

  • Individual presynaptic stimuli are frequently too small to reach the $-55\,mV$ threshold independently.

  • Summation is the process of adding subthreshold electrical potentials together to reach threshold and trigger an action potential.

• Temporal Summation:

  • Generated by a single presynaptic synapse firing high-frequency impulses in rapid succession.

  • Successive signals arrive before earlier signals decay, accumulating over time to reach $-55\,mV$ threshold.

  • Reaches threshold slightly slower than spatial summation.

• Spatial Summation:

  • Generated by multiple separate presynaptic synapses firing simultaneously onto a single postsynaptic neuron.

  • Potentials from different physical locations add together to reach $-55\,mV$ threshold.

  • Reaches threshold and triggers action potential faster than temporal summation.

Major Neurotransmitters and Functional Roles

• Acetylcholine ($ACh$):

  • Major neurotransmitter functioning in neuromuscular and cardiac tissues.

  • Excitatory Effect: Causes contraction in skeletal muscle tissue.

  • Inhibitory Effect: Slows and regulates heart rate in cardiac tissue.

• Dopamine:

  • Known as the pleasure neurotransmitter operating within the brain reward system.

  • Operates via inhibitory mechanisms to mediate feelings of pleasure associated with eating, shopping, and reward-seeking behaviors.

• Gamma-Aminobutyric Acid (GABA):

  • Primary inhibitory neurotransmitter in the brain.

  • Opens $Cl^-$ channels to generate IPSPs.

• Glutamate:

  • Primary excitatory neurotransmitter in the central nervous system.

  • Released by gustatory (taste) receptor cells to convey taste signals to the brain during sensory processing.

• Glycine:

  • Inhibitory neurotransmitter operating within central nervous system pathways.

• Norepinephrine (Noradrenaline) & Epinephrine (Adrenaline):

  • Key neurotransmitters of the sympathetic nervous system ("fight-or-flight" response).

  • Execute stimulatory, excitatory, or inhibitory regulation to control sympathetic physiological responses.

• Serotonin:

  • Regulates mood, appetite, sleep, and pain pathways.

  • Operates primarily via inhibitory mechanisms.

  • Abnormally low serotonin levels are clinically linked to Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder.