Lab 4 – Nerve Cells and Electrical Signaling

Overview

To comprehend the functioning of electrically active cells, such as neurons and muscles, it is essential to understand the driving forces acting on ions.  This knowledge clarifies why specific transport mechanisms are employed for particular substances in distinct locations.  A grasp of these concepts is crucial for determining the appropriate IV solutions and understanding the mechanisms of drug action, both of which depend on the transport and diffusion of substances in and out of cells.

Electrochemical Gradient

The intracellular compartment contains higher concentrations of solutes like K+, amino acids, proteins, ATP, and other phosphate-containing molecules (e.g., DNA and RNA) compared to the extracellular compartment.  In contrast, the extracellular compartment typically has higher levels of Na+, HCO3-, CL-, Ca2+, and glucose.  These concentration differences create an electrochemical gradient between the two compartments.

Chemical Force

When a substance moves down its concentration gradient, the reaction releases energy (exergonic) and occurs spontaneously.  Conversely, moving a substance against its concentration gradient requires energy input (endergonic) and does not happen spontaneously.  The concentration of solutes significantly influences the energetics of a solution, as substances naturally tend to spread out (diffuse).  Therefore, the greater the concentration, the stronger the tendency for diffusion.

The direction of the chemical driving force is always down the concentration gradient, from higher to lower concentration.  You can visualize this gradient as “pushing” particles to spread out.  The magnitude of the chemical driving force is proportional to the concentration gradient: the larger the difference in concentration, the greater the energy driving the substance to diffuse.

Electrical Force

An ion is a charged chemical, with cations being positively charged and anions being negatively charged.  Voltage, or the separation of charges, is maintained across the cell membrane, creating a membrane potential (Vm).  The intracellular compartment (ICF) typically has a net negative charge, while the extracellular compartment (ECF) has a net positive charge.  This separation acts like a battery, providing a potential difference that can drive work when charges move through the membrane (current).

The Na+/K+ pump uses ATP to pump 3 Na+ ions out and 2 K+ ions into the cell, resulting in a net positive charge outside.  Additionally, there are more K+ leak channels than Na+ leak channels, enhancing the negative charge inside the cell.  The membrane potential, typically around -70 mV, is crucial for cellular function.

The membrane potential generates an electrical driving force because like charges repel and opposite charges attract.  The magnitude of this force depends on:

1. The size of the membrane potential.
2. The charge (valence) of the ion.

Total Driving Force: Electrochemical Force

The total driving force acting on ions is the sum of the chemical and electrical forces.  If as substance is not an ion, only the chemical force applies.  For ions, the electrochemical force is calculated by considering both the concentration gradient and membrane potential.

Determining Electrochemical Force

To find the direction and magnitude of the electrochemical force, compare the ion’s equilibrium potential to the membrane potential (-70 mV):

• If they are the same, the ion is equilibrium with no net force acting on it.
• If different, the ion will move in the direction that balances the membrane potential to its equilibrium potential. The magnitude of the force is the voltage difference.

Examples:

• For Na+ (equilibrium potential +60 mV), the membrane potential would need to shift from -70 mV to +60 mV, driving Na+ into the cell. The magnitude of this force is 130 mV.

By understanding these forces, we can predict ion movement and its impact on cellular function.

The Nervous System

There are two main classes of cells in the nervous system: neurons and glial cells.  Neurons are the fundamental functional units and are excitable, meaning they can produce action potential (Aps).  Action potentials are large, rapidly changing electrical signals.  Neurons are highly specialized cells.  Glial cells, which make up the majority of the nervous system, are essential for maintaining normal neuronal function.  There are four types of glial cells: oligodendrocytes, Schwann cells, astrocytes, and microglia.

Neuronal Structure

A neuron can be divided into three main functional parts:

1. Cell Body (Soma): The cell body contains the nucleus and organelles, carrying out normal metabolic functions. It receives input in the form of neurotransmitters and has numerous ligand-gated receptors.
2. Dendrites: Dendrites are small branches extending from the soma, specialized to receive input in the form of neurotransmitters. They have many ligand-gated receptors.
3. Axon: The axon is a long strand of plasma membrane specialized for transmitting information. Most neurons have one main axon that can branch into collateral axons, allowing information transmission to multiple sites.  The axon hillock, where the axon originates from the cell body, is specialized to initiate potentials.  The axon terminal at the end of the axon releases neurotransmitters in response to action potentials.

Major Channel Types in Neurons

• Leak Channels (Nongated channels): Found throughout the neuron and always open, maintaining the resting potential.
• Ligand-Gated Channels: Open/close in response to specific ligand binding (often a neurotransmitter). These channels are dense on the cell body and dendrites.
• Voltage-Gated Channels: Open/close in response to changes in membrane potential. Voltage-gated Na+ and K+ channels are densely packed on the axon, especially at the hillock. Voltage-gated Ca2+ channels, mainly at the axon terminal, open is response to action potentials and trigger neurotransmitter release.

Neurons are 25 times more permeable to K+ than Na+ due to more K+ leak channels, making the resting membrane potential closer to the K+ equilibrium potential (-94 mV) than the Na+ equilibrium potential (+60 mV). Neither ion reaches equilibrium because the Na+/K+ pump continuously maintains the gradients, ensuring neural stability.  At rest, K+ leaks out, and Na+ leaks in, but the Na+/K+ pump compensates for these leaks by actively transporting K+ back in and Na+ out.

Electrical Signaling through Changes in Membrane Potential (Vm)

Gated ion channels open or close in response to stimuli, allowing specific ions to move and change the membrane potential towards the equilibrium potential for that ion. There are three types of gated ion channels in humans:

1. Voltage-Gated Channels: Open/close in response to voltage changes.
2. Ligand-Gated Channels: Open/close in response to chemical signals (typically neurotransmitters).
3. Mechanically-Gated Channels: Open/close in response to mechanically stress, associated with sensory responses.

Changes in membrane potential are named based on their direction relative to the resting potential (-70 mV):

Depolarization: Membrane potential become less negative or fully positive.

Hyperpolarization: Membrane potential becomes more negative.

Repolarization: Membrane potential returns to resting state.

There are two main types of electrical signals in neurons due to gated ion channel activity:

1. Graded Potentials (GPs):

• Small, short-range, and decrease in size over distance.
• Often result from neurotransmitter binding to ligand-gated receptors on dendrites.
• Magnitude is proportional to stimulus strength (graded).
• Can be hyperpolarizing (inhibitory) or depolarizing (stimulatory).
• Determine if an action potential will be generated, requiring the graded potential to reach a threshold level.
• Decrease in strength with distance due to current loss through leak channels.

2. Action Potentials (APs):

• Large, long-range, and do not decrease in size.
• All-or-nothing events; they either occur fully or not at all.
• Comprise three phases: depolarization, repolarization, and after-hyperpolarization.

Phases of an Action Potential:

1. Depolarization: Membrane potential changes from -70 mV to +30 mV due to Na+ permeability increase.
2. Repolarization: Membrane potential returns to -70 mV as Na+ permeability decreases and K+ permeability increases.
3. After-Hyperpolarization: Membrane potential briefly becomes more negative than the resting potential due to slow closure of K+ channels.

Refractory Periods:

Absolute Refractory Period: Lasts 1-2 ms, during which another AP cannot be generated.

Relative Refractory Period: Lasts 5-15 ms, during which a suprathreshold stimulus can generate another AP.