Study Notes for Electrophysiology of Neurons: Part I

Chapter 11: Electrophysiology of Neurons: Part I

Ion Channels

  • Definition of Ion Channels:
      - Transmembrane proteins in the plasma membrane.
      - Facilitate specific ions' movement into/out of the cell.
  • Categories of Ion Channels:
      1. Leak Channels:
         - Always open, allowing continuous current to pass through.
      2. Gated Channels:
         - Closed unless stimulated to open.
         - No current (ions) flow when closed.

Classes of Gated Ion Channels

  • Chemically (Ligand)-Gated Channels:
      - Open when a ligand (extracellular chemical messenger) binds to the receptor region.
      - Specific chemical compatibility is required for opening the channel.
      - Neurotransmitters do not pass through; they only function to open the channel.

  • Voltage-Gated Channels:
      - Open due to membrane potential depolarization.
      - Special note on a channel that opens during hyperpolarization in cardiac physiology.

  • Mechanically-Gated Channels:
      - Open due to mechanical stimuli like stretch or pressure.
      - Example: "Ketchup bottle" – pressure required to open.

Resting Membrane Potential of Neurons

  • Polarization of Neurons:
      - Neurons maintain an electric charge due to different distributions of ions (positive and negative) across the membrane.
      - Membrane potential: potential difference created, analogous to a battery.
      - Voltage measured in millivolts (mV); typical resting membrane potential (RMP) in neurons is approximately -70 mV.

Concentration Gradients of Na+ and K+

  • Key Role of Concentration Gradients:
      - Na+/K+ pumps maintain concentration differences of Na+ and K+:
        - Intracellular fluid (ICF): 150 mM K+, 15 mM Na+
        - Extracellular fluid (ECF): 5 mM K+, 150 mM Na+
  • Importance of K+ Leak Channels:
      - K+ leaves the cell down the concentration gradient, contributing to the negative charge of the cell.
  • Ratio of Leak Channels:
      - 25 K+ channels for every 1 Na+ channel; ensures more K+ leaves than Na+ enters, maintaining the negative RMP.

Summary of RMP Factors

  • Key Factors Determining RMP:
      1. Unequal ion distribution across the plasma membrane.
      2. Large negatively charged proteins (anions) trapped in the cell.
      3. Na+/K+ pump function (3 Na+ out for every 2 K+ in).

Electrical Signals Created by the Movement of Ions

  • Membrane polarization allows neurons to receive, integrate, and transmit information.
  • Changes in membrane potential:
      - Depolarization: Less negative than RMP.
      - Hyperpolarization: More negative than RMP.

Types of Electrical Signals

  • Graded Potentials (GPs):
      - Mediated by ligand-gated or mechanically-gated channels.
      - Initiated in dendrites or soma via synaptic input.
      - Local changes in membrane potential that rapidly decay.
      - Vary directly with stimulus strength.
  • Action Potentials (APs):
      - Mediated by voltage-gated channels.
      - Follow the all-or-none principle: if threshold is reached, AP occurs.
      - Rapid, large change in membrane potential.
      - Do not decay over distance; constant strength from axon hillock to synaptic terminal.

Voltage-Gated Channels and Action Potentials

  • Types of voltage-gated channels involved in action potentials:
      1. Voltage-Gated Na+ Channel:
         - Three states: closed, open (activated), and inactivated.
      2. Voltage-Gated K+ Channel:
         - Two states: closed and open (activated).

Kinetics of Voltage-Gated Channels

  • Voltage-Gated Na+ Channels:
      - Fast opening and closing, likened to sports cars.
      - TTX (Tetrodotoxin) can block these channels; lethal doses very low.

  • Voltage-Gated K+ Channels:
      - Slower to open and close, likened to semi trucks.
      - TEA (Tetraethylammonium) used to block these channels in lab settings.

Threshold Potential

  • To initiate an action potential, membrane potential must reach threshold (~ -55 mV).
  • Depolarization to threshold typically occurs due to graded potentials resulting from synaptic activity.

Phases of Action Potential

  • Phases:
      1. Depolarization: Rapid Na+ influx upon reaching threshold, potential rises to +30 mV.
      2. Repolarization: Na+ channels inactivate while K+ channels open, allowing K+ efflux back to resting levels.
      3. Hyperpolarization: Membrane potential briefly overshoots RMP due to continued K+ efflux (drops to -90 mV) before returning to -70 mV.

Summary of Action Potential Phases

  • Summary of phases illustrates key events in Na+ and K+ channel activity during the AP.
  • Refractory Periods:
      - Absolute Refractory Period: Na+ channels inactivated, no AP can occur regardless of stimulus.
      - Relative Refractory Period: Na+ channels reset, K+ channels still open, requires stronger stimulus to initiate AP (suprathreshold).

Action Potential Propagation

  • Conduction Velocities: Determined by:
      1. Axon Diameter: Larger diameter reduces resistance and increases speed.
      2. Myelin Sheath: Presence enhances conduction speed, allows saltatory propagation (faster than contiguous).
  • Contiguous Propagation: In unmyelinated axons, the entire axon propagates AP.
  • Saltatory Propagation: Myelinated axons propagate AP quickly via Nodes of Ranvier, likened to "charging pads" in games.

Synapses

  • Types of synapses:
      1. Electrical Synapses: Fast ion movement through gap junctions; synchronize cell activity.
      2. Chemical Synapses: Information transfer through neurotransmitters from presynaptic to postsynaptic neurons.

Chemical Synapse Events

  1. Action potential arrives at presynaptic neuron.
  2. Ca2+ channels open, Ca2+ influxes, triggering neurotransmitter release.
  3. Neurotransmitters diffuse across synaptic cleft and bind to postsynaptic receptors.
  4. Ion channels open, resulting in graded potential.
  5. Termination of neurotransmitter effect by reuptake, enzymatic degradation, or diffusion.

Postsynaptic Potentials

  • Changes in postsynaptic cell's membrane potential due to ion channel opening.
  • Two types of postsynaptic potentials:
      1. EPSP (Excitatory Postsynaptic Potential): Depolarizes, moves closer to threshold, usually mediated by glutamate.
      2. IPSP (Inhibitory Postsynaptic Potential): Hyperpolarizes, moves away from threshold, often mediated by GABA.

Neurotransmitter Receptors

  • Binding of neurotransmitters activates two types of receptors:
      1. Ion Channel-Linked Receptors: Rapid effect by opening ion channels.
      2. G-Protein Coupled Receptors (GPCRs): Activate intracellular signaling pathways leading to longer-lasting effects.

Second Messenger Pathways

  • cAMP Pathway: Common second messenger pathway activated by GPCRs, influences heart rate and bronchial dilation.

Types of Neurotransmitters

  • About 50 neurotransmitters identified; focus on key ones:
      - Acetylcholine (ACh): First identified neurotransmitter, involved in muscle activation and neurotransmission.
      - Biogenic Amines: Include dopamine (pleasure), norepinephrine, and serotonin (mood).
      - Amino Acids: Glutamate (excitatory), glycine (inhibitory), GABA (inhibitory).
      - Neuropeptides: Substances such as endorphins and substance P (pain).
      - Purines: Adenosine (inhibitory in brain, caffeine blocks receptors).
      - Gases/Lipids: Nitric oxide (cell signaling), endocannabinoids (modulate neuronal activity).

Developmental Aspects of Neurons

  • Neural development involves competition for resources, leading to apoptosis (cell death) of unconnected axons.
  • Neurons generally do not undergo mitosis post-birth; exceptions exist in some brain areas (e.g., olfactory and hippocampal neurons).
  • Plasticity refers to the ability to change based on experience, particularly acute in early life stages.