Teaching pharmacodynamics: Building a hands-on neurotransmitter / receptor binding demonstration
This is a hands-on demonstration that can be used in a lecture outlining the principles of pharmacodynamics. Through this short 10-15 minute simulation, students will learn that:
The binding of a neurotransmitter to its receptor is a stochastic, random process
Increases in neurotransmitter release can increase likelihood of binding, and decreases in release decrease binding probability
The ligand-receptor interaction can be modified by molecules of competitive antagonist present in the synapse
Upregulation and downregulation of receptor levels change signaling strength, even without changing the number of neurotransmitter molecules released
In this demonstration, you will build small, palm-sized boxes that represent synapses after the release of neurotransmitters. Within each box are plastic beads and a foam cutout with holes. Each bead within the box represents a single molecule of neurotransmitter. Each hole in the foam represents a single receptor, specifically the active site of that receptor.
Students can be divided into groups, and each group should be given all the boxes necessary to complete this demonstration. I have found that groups of three to five students works well.
Building the boxes
Materials:
Cardboard jewelry boxes. These can be bought online or at a local crafts store. The height should be at least 1 inch. The length and width dimensions are not too critical; the size I use in my classes is 2.5 x 2.5 inches. These can be labeled on the top as to which “scenario” each box simulates, or can be decorated, as one of my students did to mine recently after the release of Squid Game.
Foam sheet. It’s hard to find this stuff to purchase. Most packing styrofoam that breaks apart into large balls won’t work too well, but sometimes you’ll get the Good Stuff in deliveries. It’s easy to repurpose this packing material for these boxes. As for thickness, it would be best if it were a fourth or a third of the height of the box to give the beads room to roll around.
Beads. Buy these online, at a crafts shop, or steal them from children (preferably, your own children.) You’ll want to get some extra - historically, I’ve lost about 1 bead per demonstration.
Assembly procedure:
Cut packing material foam into squares to fit into the bottom of each box. It should be a very tight squeeze side to side, so that the foam will not come loose after shaking or inverting.
Cut a number of holes (I use 9), approximately the same diameter as the beads, into the foam. These represent the active site of receptors.
Put 10 beads into each box. These represent molecules of neurotransmitter.
Give students the following steps when performing the simulation in class:
Remove all beads from the box, shaking them loose into your hand or into the lid of the box.
Return beads into the box, put the lid on the box, and shake for a few seconds.
Open the lid, count the number of holes with a bead in it, and record this number.
Repeat for each box.
Each student will collect data for each box.
Average your group data for each condition.
Consider using different boxes to simulate different scenarios.
In the presence of a competitive antagonist. Here, in addition to the 10 beads, include 5 beads of a different color. Tell students, when counting beads, to not count any holes containing a bead of a different color. These other beads represent moments when the active site is bound by a competitive antagonist rather than an agonist. On average, these counts will be lower than the baseline condition.
During high release circumstances, or in the presence of a reuptake inhibitor or inhibitor of a degradation enzyme. Instruct students to include 15 beads before shaking boxes, rather than the baseline of 10. This represents moments where many neurotransmitters are released (increase of activity presynaptically, or artificially induced high frequency stimulation). This could also represent the synapse when reuptake inhibitors or inhibitors of degradation enzymes are present, as there are now more molecules in the synapse capable of binding to the receptors. On average, these counts will be higher than baseline.
During low release circumstances, such as in the presence of modifiers of the SNARE complex, presynaptic calcium channel inhibitors, or calcium chelators. For these conditions, have students include only 5 beads instead of 10 before shaking. With less synaptic release, there will be fewer molecules of neurotransmitter in the synapse, so on average, these counts will be lower than baseline.
Following desensitization or sensitization, or long term plasticity phenomena. These boxes require a different foam cutout. In the case of desensitization or receptor downregulation, only make 5 holes to represent fewer receptors available for binding. On average, these counts will be lower than baseline. To model sensitization or receptor upregulation, make 12 or 15 holes to represent more receptors available. On average, these counts will be higher than baseline.
Instructor notes:
Yes, I am aware Excel data visualization is a horrendous sin.
Make sure to stress ”number of holes with a bead in it.” In previous iterations of the class, students recorded the number of beads that fell into the holes, which is not an accurate representation of the nature of neurotransmitter-receptor interactions. These counts also could artificially inflate numbers and skew data collection.
A common misconception I have seen in Introductory Neuroscience courses about the action of classical neurotransmitters is that they enter into the postsynaptic cell. Use this demonstration to further stress the point that the beads pass on their signal by filling the hole, not “entering through the box.”
Occasionally, some students will report numbers that are not as expected. This is a good moment to reinforce the premise that ligand-receptor binding events are random, but influenced by probability. Compare these outlier data points with trends across the class to show that the means are overall more representative than individual data points.
Collect data from across classes. Build a spreadsheet with historical data to allow students to see how their data compares with previous classes. In every one of the six classes I have used this specific demonstration, class data trended in the same direction.
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Happy Teaching!