What are the two mechanisms by which a neurotransmitter binding its receptor can result in a change in the membrane potential of the postsynaptic cell?

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 Figure. 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.

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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 Table. The difference in the number of positively charged potassium ions (K+) inside and outside the cell dominates the resting membrane potential (Figure). 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.

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 and Figure). 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.

Art Connection

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?

Link to Learning

This video presents an overview of action potential.

Myelin and the Propagation of the Action Potential

For an action potential to communicate information to another neuron, it must travel along the axon and reach the axon terminals where it can initiate neurotransmitter release. The speed of conduction of an action potential along an axon is influenced by both the diameter of the axon and the axon’s resistance to current leak. Myelin acts as an insulator that prevents current from leaving the axon; this increases the speed of action potential conduction. In demyelinating diseases like multiple sclerosis, action potential conduction slows because current leaks from previously insulated axon areas. The nodes of Ranvier, illustrated in Figure are gaps in the myelin sheath along the axon. These unmyelinated spaces are about one micrometer long and contain voltage gated Na+ and K+ channels. Flow of ions through these channels, particularly the Na+ channels, regenerates the action potential over and over again along the axon. This ‘jumping’ of the action potential from one node to the next is called saltatory conduction. If nodes of Ranvier were not present along an axon, the action potential would propagate very slowly since Na+ and K+ channels would have to continuously regenerate action potentials at every point along the axon instead of at specific points. Nodes of Ranvier also save energy for the neuron since the channels only need to be present at the nodes and not along the entire axon.