Introduction

How many electrical devices do you have on you at the moment?

Electrical circuits are everywhere, I have my tablet, tablet pen, the remote, the microphone, my phone, and my watch. I’ve got six different electrical circuits on me right now.

There are a lot of things that you might not think of as being an electric circuit, but we can analyze using the properties of circuits, which we are going to discuss over the course of this unit.

By the end of this unit, we will be able to draw a rough circuit and think about a neuron as a circuit. A cell membrane is essentially a capacitor, so we can think about cell membrane ion transport, so we’ll be able to talk a little bit about cell membranes in this context.

We will introduce what a current is but other than that there are not a lot of new fundamental physics in this unit, we’re mostly going to be dealing with the idea that if I put a charge and a potential, I get a potential energy. That is going to be the vast majority of what we’re going to be working with. It’s really a lot of application of those ideas and seeing how things work.

Motivating Biological Context for Unit IV – The Neuron

All functions performed by the nervous system—from a simple motor reflex to more advanced functions like making a memory or a decision—require neurons to communicate with one another. While humans use words and body language to communicate, neurons use electrical and chemical signals. Just like a person in a committee, one neuron usually receives and synthesizes messages from multiple other neurons before “making the decision” to send the message on to other neurons.

Nerve Impulse Transmission within a Neuron

For the nervous system to function, neurons must be able to send and receive signals. These signals are possible because each neuron has a charged cellular membrane (a voltage difference between the inside and the outside), and the charge of this membrane can change in response to neurotransmitter molecules released from other neurons and environmental stimuli. To understand how neurons communicate, one must first understand the basis of the baseline or ‘resting’ membrane charge.

Neuronal Charged Membranes

The lipid bilayer membrane that surrounds a neuron is impermeable to charged molecules or ions. To enter or exit the neuron, ions must pass through special proteins called ion channels that span the membrane. Ion channels have different configurations: open, closed, and inactive, as illustrated in the figure below. Some ion channels need to be activated in order to open and allow ions to pass into or out of the cell. These ion channels are sensitive to the environment and can change their shape accordingly. Ion channels that change their structure in response to voltage changes are called voltage-gated ion channels. Voltage-gated ion channels regulate the relative concentrations of different ions inside and outside the cell. The difference in total charge between the inside and outside of the cell is called the membrane potential.

This video discusses the basis of the resting membrane potential.

Resting Membrane Potential

A neuron at rest is negatively charged: the inside of a cell is approximately 70 millivolts more negative than the outside (−70 mV, note that this number varies by neuron type and by species). This voltage is called the resting membrane potential; it is caused by differences in the concentrations of ions inside and outside the cell. If the membrane were equally permeable to all ions, each type of ion would flow across the membrane and the system would reach equilibrium. Because ions cannot simply cross the membrane at will, there are different concentrations of several ions inside and outside the cell, as shown in the table below. The difference in the number of positively charged potassium ions (K⁺) inside and outside the cell dominates the resting membrane potential (figure below table). When the membrane is at rest, K⁺ ions accumulate inside the cell due to a net movement with the concentration gradient. The negative resting membrane potential is created and maintained by increasing the concentration of cations outside the cell (in the extracellular fluid) relative to inside the cell (in the cytoplasm). The negative charge within the cell is created by the cell membrane being more permeable to potassium ion movement than sodium ion movement. In neurons, potassium ions are maintained at high concentrations within the cell while sodium ions are maintained at high concentrations outside of the cell. The cell possesses potassium and sodium leakage channels that allow the two cations to diffuse down their concentration gradient. However, the neurons have far more potassium leakage channels than sodium leakage channels. Therefore, potassium diffuses out of the cell at a much faster rate than sodium leaks in. Because more cations are leaving the cell than are entering, this causes the interior of the cell to be negatively charged relative to the outside of the cell. The actions of the sodium potassium pump help to maintain the resting potential, once established. Recall that sodium potassium pumps brings two K⁺ ions into the cell while removing three Na⁺ ions per ATP consumed. As more cations are expelled from the cell than taken in, the inside of the cell remains negatively charged relative to the extracellular fluid. It should be noted that chloride ions (Cl^–) tend to accumulate outside of the cell because they are repelled by negatively-charged proteins within the cytoplasm.

Ion Concentration Inside and Outside Neurons
Ion	Extracellular concentration (mM)	Intracellular concentration (mM)	Ratio outside/inside
Na+	145	12	12
K+	4	155	0.026
Cl−	120	4	30
Organic anions (A−)	—	100

The resting membrane potential is a result of different concentrations inside and outside the cell.

Action Potential

A neuron can receive input from other neurons and, if this input is strong enough, send the signal to downstream neurons. Transmission of a signal between neurons is generally carried by a chemical called a neurotransmitter. Transmission of a signal within a neuron (from dendrite to axon terminal) is carried by a brief reversal of the resting membrane potential called an action potential. When neurotransmitter molecules bind to receptors located on a neuron’s dendrites, ion channels open. At excitatory synapses, this opening allows positive ions to enter the neuron and results in depolarization of the membrane—a decrease in the difference in voltage between the inside and outside of the neuron. A stimulus from a sensory cell or another neuron depolarizes the target neuron to its threshold potential (-55 mV). Na⁺ channels in the axon hillock open, allowing positive ions to enter the cell (figure above and graph below). Once the sodium channels open, the neuron completely depolarizes to a membrane potential of about +40 mV. Action potentials are considered an “all-or nothing” event, in that, once the threshold potential is reached, the neuron always completely depolarizes. Once depolarization is complete, the cell must now “reset” its membrane voltage back to the resting potential. To accomplish this, the Na⁺ channels close and cannot be opened. This begins the neuron’s refractory period, in which it cannot produce another action potential because its sodium channels will not open. At the same time, voltage-gated K⁺ channels open, allowing K⁺ to leave the cell. As K⁺ ions leave the cell, the membrane potential once again becomes negative. The diffusion of K⁺ out of the cell actually hyperpolarizes the cell, in that the membrane potential becomes more negative than the cell’s normal resting potential. At this point, the sodium channels will return to their resting state, meaning they are ready to open again if the membrane potential again exceeds the threshold potential. Eventually the extra K⁺ ions diffuse out of the cell through the potassium leakage channels, bringing the cell from its hyperpolarized state, back to its resting membrane potential.

 

Potassium channel blockers, such as amiodarone and procainamide, which are used to treat abnormal electrical activity in the heart, called cardiac dysrhythmia, impede the movement of K⁺ through voltage-gated K⁺ channels. Which part of the action potential would you expect potassium channels to affect?

Homework

1. Which ions are important in understanding neuron function?