BIPN 100 - B1 Prelecture 2

Membrane Dynamics

• Basis for electrical signals in the nervous system.

Neural Membrane

• Impermeable to ions due to the bilipid layer (phospholipid bilayer).

• Semipermeable due to ion channels.

• Ions can only cross the membrane through ion channels.

Ion Channels

• Membrane proteins with selective permeability.

• Allow only specific ions to pass through based on amino acid moieties and pore shape.

• Types of channels:

  • Leak channels:

    • Simplest, always open.

    • Pass single types of ions.

  • Voltage gated ion channels:

    • Open and close in response to changes in membrane potential (voltage difference between inside and outside of the cell).

    • Changes in voltage affect charged amino acids, physically opening or closing the channel.

  • Ligand gated ion channels:

    • Open upon binding of a neurotransmitter (e.g., serotonin, dopamine, glutamate).

    • Neurotransmitter binding causes a conformational change that allows ions to pass.

Resting Membrane Potential

• The difference in electrical charge (voltage) between the inside and outside of the cell.

• Voltage is always a measurement between two points (reference electrode and measurement point).

• Analogous to potential energy (e.g., ball at the top of a hill).

• Terms: membrane potential = membrane voltage (VM).

• Defined as the inside of the cell relative to the outside (reference). Outside is typically the "zero" point.

• Typically, the inside of the cell is negative at resting membrane potential.

• Units: volts or millivolts (typically millivolts in neurobiology).

• Requires a reference and measurement point setup using electrophysiology.

  • Intracellular recording: electrode inside the cell, reference electrode outside.

Ion Concentrations

• Concentrations of potassium (K+), sodium (Na+), and chloride (Cl-) determine the neural membrane potential.

• Potassium (K+):

  • High concentration inside the cell (intracellular).

  • Low concentration outside the cell (extracellular).

• Sodium (Na+):

  • Low concentration inside the cell (intracellular).

  • High concentration outside the cell (extracellular).

• Chloride (Cl-):

  • Low concentration inside the cell (intracellular).

  • High concentration outside the cell (extracellular).

• Calcium (Ca2+):

  • Much higher outside than inside.

  • Low intracellular calcium concentration due to calcium phosphate formation and binding to calcium binding proteins.

• Concentrations are measured in millimolar (mM), denoted by brackets $[]$.

Resting Membrane Potential (cont.)

• The stable voltage of a quiescent cell not firing an action potential.

• No net movement of charge (ions moving in and out are equal).

• Typically -60 to -70 mV in most neurons.

Sodium-Potassium ATPase

• Maintains concentration gradients.

• Exchanges three sodium ions (Na+) out of the cell for two potassium ions (K+) into the cell.

• Requires ATP hydrolysis.

• Maintains resting membrane potential by keeping extracellular sodium high and intracellular potassium high.

• Uses a significant amount of energy (20-30% of a neuron's energy).

• Antiport: carrier protein that moves substances in opposite directions.

• Active transporter: uses ATP to move ions against their concentration gradients.

Electrochemical Gradient

• Combination of concentration gradient and electrical gradient.

• Electrical driving force: attraction or repulsion between charged particles.

• Chemical driving force: diffusion from high to low concentration.

• Driven by entropy: tendency to move from high energy to low energy (more disordered) state.

Membrane Permeability

• Differences in membrane permeability are critical for setting up concentration gradients.

• Selective permeability: only certain ions can pass through specific ion channels.

• Permeability is determined by the number of ion channels for a specific ion.

• At rest, the membrane is more permeable to potassium (K+) due to more potassium leak channels.

Ion Movement and Forces

• Potassium (K+) wants to move out of the cell due to its high concentration inside, but the negative charge inside the cell exerts an electrical force pulling it in, so there's also an electrical force coming in.

Nernst Equation and Equilibrium Potential

• Equilibrium is reached when the concentration gradient is balanced (equal and opposite) by the electrical force.

• To analyze ion movement:

  • Know the concentration gradient (high inside vs. high outside).

  • Know the charge of the ion (positive or negative).

  • Know the voltage of the membrane (inside vs. outside).

• Equilibrium potential (Eion): the point at which the electrical and chemical forces are equal and opposite, resulting in no net ion movement.

• Relates differences in entropic states of ion concentration and electrical gradient.

Nernst Equation Derivation

• At equilibrium, the sum of electrical and chemical potentials is zero, so we derive the Nernst equation by combining the equations for electrical and chemical potentials and setting them equal.

• $E<em>{ion} = \frac{RT}{zF} \ln{\frac{[ion]</em>{outside}}{[ion]_{inside}}}$

• Where:

  • $E_{ion}$ is the equilibrium potential for a specific ion.

  • $R$ is the gas constant.

  • $T$ is the temperature in Kelvin.

  • $z$ is the ion's charge (valence).

  • $F$ is the Faraday constant.

• Simplified equation (at room temperature):

  • $E<em>{ion} = \frac{61}{z} \log{\frac{[ion]</em>{outside}}{[ion]_{inside}}}$

  • where 61 is a constant combining multiple values.

The equation tells you the voltage for a specific ion at which you're gonna see an equilibrium potential.