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The resting membrane potential is the stable, negative electrical charge inside a neuron relative to the outside when it is not actively signaling, typically around -65 mV. This potential is established by an unequal distribution of ions across the cell membrane. At rest, sodium (Na+) ions are more concentrated in the extracellular fluid, while potassium (K+) ions and large negatively charged proteins (anions) are more concentrated in the cytoplasm. This separation of charges causes ions to accumulate near the membrane, attracted to the opposite charges on the other side. The potential is actively maintained by the sodium-potassium pump, which expels three Na+ ions for every two K+ ions it brings in, contributing to the net negative charge inside the neuron.

Resting Membrane Potential

The Nernst equation predicts the membrane potential at which the processes of diffusion and the active transport of the sodium-potassium pump reach equilibrium. The Nernst equation can therefore help to predict the resting membrane potential. However, it is not very accurate because it does not take into account how the selective permeability of the cellular membrane to each ion affects the membrane potential, as with the Goldman equation. The Nernst Equation is given by the following: 58/(electrical charge ion x in millivolts (mV)) X log((concentration of x outside)/(concentration of x inside)).  

Nernst Equation

While there are many ways to measure membrane potential, two common ways are known as voltage clamping and patch clamping. 

1.) Voltage Clamping: Voltage clamping is the process of "clamping" or setting the membrane potential to match a particular voltage, known as the "command potential." This is accomplished by placing an electrode into the interior of the axon that measures the membrane potential of the axon. This electrode is connected to a voltmeter, which measures the potential difference between the interior of the axon and the surroundings of the axon. Finally, information about the potential difference (i.e., membrane potential) is sent to a voltage clamp amplifier, which compares the current membrane potential with the command potential and "injects" current such that the membrane potential matches the command potential. 

2.) Patch Clamping: Voltage clamping can not only help us set a membrane potential, but it can also tell us how much current is flowing through Na+ ion channels during an action potential. A more precise way to measure this might be through patch clamping. A patch clamp uses a voltage clamp to measure the flow of current through a tiny patch of membrane. There are many different patch clamping techniques that can be used to measure currents pulsing through different patches of membrane, from whole cellular membrane to a single receptor on the cellular membrane. 

Measuring Membrane Potential

An especially small conductor used to record electrical signals from a cell.

Microelectrode

The Goldman equation predicts the potential difference across a membrane based on the concentrations of ions, inside the cell, outside the cell, and the permeability of the the membrane.

Goldman Equation

The sodium-potassium pump is an active transport mechanism in the neuronal membrane that is crucial for maintaining the resting potential. It works by continuously moving ions against their concentration gradients, expelling three positively charged sodium ions (Na+) from the cell for every two positively charged potassium ions (K+) it imports. This unequal exchange of positive ions results in a net loss of positive charge from the neuron's interior, thereby creating the net negative charge inside the cell.

Sodium-Potassium Pump

During the resting state, two main forces act on ions across the neuronal membrane. The first is diffusion, where ions move down their concentration gradient. Specifically, sodium (Na+), being more concentrated outside the cell, is driven inward, while potassium (K+), being more concentrated inside, is driven outward. The second force is electrostatic pressure, arising from the net negative charge inside the cell. This electrical gradient provides an additional force attracting positively charged ions like sodium into the neuron.

Pressures on Ions During Resting Potential

Imagine a neuron is exposed to a substance that specifically blocks the protein pump responsible for moving three sodium ions out of the cell for every two potassium ions it moves in. Assuming ion channels still allow for some passive leakage, what would be the most likely consequence for the neuron's resting membrane potential over time?

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