Neurophysiology Powerpoint

BIOL 2401: Anatomy & Physiology 1 - Nervous System - Neurophysiology Module 10 Part I and II

Electrophysiology of Neurons: Part I

Ion Channels

• Definition: A transmembrane protein in the plasma membrane that allows specific ions to move into or out of the cell.

• Categories:

  • Leak Channels: Always open, allowing ion current to pass continuously.

  • Gated Channels: Open in response to a specific stimulus, and close otherwise.

• Types of Gated Channels: Introduced in subsequent slides.

Classes of Gated Ion Channels

1. Chemically (ligand)-gated Ion Channels:

   • Function: Open when a ligand (an extracellular chemical messenger) binds to the receptor region of the channel.

2. Voltage-gated Ion Channels:

   • Function: Open when the membrane undergoes depolarization. (Note: There is one channel that opens upon hyperpolarization related to cardiac function.)

3. Mechanically-gated Ion Channels:

   • Function: Opened by mechanical stimuli such as stretch or pressure.

Resting Membrane Potential of Neurons

• Definition: Neurons, like all cells, are polarized, creating an electric charge due to the differential distribution of positive and negative charges across the plasma membrane.

• Membrane Potential: Refers to the potential difference across the plasma membrane.

  • Voltage Measurement: Measured in volts (V) but small voltages in cells are typically measured in millivolts (mV).

  • Typical RMP of neurons: Approximately -70mV.

Concentration Gradients of Na+ and K+

• Na+/K+ Pumps: All cells possess these pumps that actively transport Na+ and K+ ions.

  • Activity: Pumps Na+ out of the cell into extracellular fluid (ECF) and K+ into the intracellular fluid (ICF).

  • Average Concentration:

  • ICF:

    • K+: 140 mM

    • Na+: 15 mM

  • ECF:

    • K+: 5 mM

    • Na+: 140 mM

Electrochemical Gradient of Ions

• Gradient Overview: The concentration gradient typically drives solute diffusion; however, charged ions also experience an electrical gradient due to interactions with local charges.

• Electrochemical Gradient: Formed by the combination of concentration and electrical gradients, influencing the movement of ions.

Development of Resting Membrane Potential (RMP)

1. Initial State: Begin with an artificial cell experiencing an even charge distribution (0 mV membrane potential).

2. Introduction of K+ Leak Channel: Allows K+ to exit the cell down its concentration gradient, resulting in a negative membrane potential.

3. Establishment of Electrical Gradient: The loss of K+ leads to a more negative membrane charge, which creates an electrical gradient opposing K+ exit.

Equilibrium Potential for Ions

• Equilibrium Potential for K+:

  • Achieved when the force of the electrical gradient equals the concentration gradient, typically around -90 mV.

• Equilibrium Potential for Na+:

  • If only Na+ permeable, the influx drives the membrane potential positive. The equilibrium potential for Na+ occurs at approximately +61 mV.

Factors Influencing Resting Membrane Potential

• In reality, both K+ and Na+ move across the membrane during resting states.

• Ion Channel Density: There are significantly more K+ channels compared to Na+ channels (25:1 ratio), resulting in a driving effect towards the equilibrium potential of K+, while slight Na+ influx keeps RMP slightly positive.

• Constant Activity of Na+/K+ Pumps: Maintains concentration gradients by continuously working against diffusion forces.

Electrical Signals Created by Ionic Movement

• Resting Membrane Potential: Neurons maintain a RMP around -70 mV.

• Types of Voltage Changes:

  • Depolarization: Results in a less negative potential (more positive).

  • Hyperpolarization: Results in a more negative potential.

Graded Potentials and Action Potentials

• Graded Potentials: Localized changes initiated in dendrites through ligand-gated channels, which decay rapidly over distance and are proportional to stimulus strength.

• Action Potentials (APs):

  • Mediated by voltage-gated channels, they are all-or-none responses with consistent magnitude. APs encompass rapid changes in membrane potential and maintain strength throughout conduction down the axon.

Voltage-Gated Channels in Action Potential

• Voltage-gated Na+ Channel: Contains an activation gate and inactivation gate leading to three possible states:

  1. Closed: Capable of opening.

  2. Open: Allows Na+ influx.

  3. Inactivated: Closed and non-responsive.

• Voltage-gated K+ Channel: Contains a single activation gate leading to states of closed and open condition influencing K+ efflux.

Threshold Potential

• Definition: The membrane potential must depolarize to approximately -55 mV to trigger an action potential.

• Triggering Mechanism: Caused by graded potentials from synaptic activity, pushing the membrane towards threshold.

Phases of Action Potential

1. Depolarization: Na+ channels open, and Na+ influx causes rapid membrane depolarization.

2. Repolarization: At the peak (~+30 mV), Na+ channels inactivate, and K+ channels open, resulting in K+ efflux that restores negative membrane potential.

3. Hyperpolarization: Membrane potential momentarily becomes more negative than -70 mV before returning to resting potential.

Refractory Periods

• Absolute Refractory Period: No action potential can be fired when Na+ channels are open or inactivated.

• Relative Refractory Period: After Na+ channels reset, another AP can be initiated only with a stronger stimulus due to K+ channels still being open.

Action Potential Propagation

• Propagation Mechanisms:

  1. Contiguous Propagation: Occurs in unmyelinated axons, where local depolarizations propagate adjacently along the axon.

  2. Saltatory Propagation: Occurs in myelinated axons, where the action potential jumps between Nodes of Ranvier, allowing for rapid conduction due to insulation.

Electrophysiology of Neurons: Part II

Synapses

• Types of Synapses:

  1. Electrical Synapses: Comprised of gap junctions allowing ionic currents to flow between adjacent cells.

  2. Chemical Synapses: Complex mechanisms involving neurotransmitter release and binding to receptors.

Chemical Synapses

Sequence of Events:

1. Arrival of an action potential at the presynaptic neuron triggers Ca2+ influx.

2. Exocytosis of neurotransmitters occurs.

3. Neurotransmitters diffuse across the synaptic cleft and bind to postsynaptic receptors.

4. Ion channels open resulting in graded potentials in the postsynaptic neuron.

5. Neurotransmitter effects are terminated through various processes.

Postsynaptic Potentials (PSPs)

• Definition: Changes in membrane potential induced by neurotransmitter effects on the postsynaptic cell.

• Types:

  1. Excitatory Postsynaptic Potential (EPSP):

     • Makes the postsynaptic membrane less negative, moving towards threshold (often caused by Na+ influx).

  2. Inhibitory Postsynaptic Potential (IPSP):

     • Moves the membrane potential further from threshold, often via K+ efflux or Cl- influx.

Removal of Neurotransmitter from Synapse

1. Diffusion and Absorption: Neurotransmitters diffuse away and are taken back by the presynaptic neuron.

2. Degradation: Neurotransmitters are broken down by enzymes in the synaptic cleft.

3. Reuptake: Presynaptic neuron reabsorbs neurotransmitter.

Summation of EPSPs

• Definition: Aggregation of EPSPs to reach the threshold potential for initiating an AP.

• Types of Summation:

  1. Temporal Summation: Rapid stimulation from a single presynaptic neuron.

  2. Spatial Summation: Simultaneous stimulation from multiple presynaptic neurons.

Neurotransmitter Receptors

• Types:

  1. Ion Channel-Linked Receptors: Mediates rapid and short-lived changes (opens upon ligand binding).

  2. G-Protein Coupled Receptors (GPCRs): Acts via intracellular G-proteins, influencing longer-lasting cellular effects.

2nd Messenger Pathways: cAMP

• One of the most prevalent second messengers derived from ATP, influencing various intracellular processes through subsequent signaling pathways.