Learning patch clamp electrophysiology from scratch: views from a learning postdoc
by Ana Dorrego-Rivas, Centre for Developmental Neurobiology
Introduction
I have been in the neuroscience field for some time now. My PhD gave me a strong neuron cell biology background and I spent most of the time playing with cultured neurons from rodents, observing and analysing them under a wide range of microscopes. However, I was intrigued by how neurons function at the physiological level, and this is how I ended up at my postdoc lab (Grubb Lab) at King’s College London, an expert group in this technique. I am currently doing only the very first steps of patch clamp, but I have already learnt valuable knowledge to transmit to beginners.
I will be honest: patch clamp electrophysiology is not the most straightforward technique to learn, even less if 1) you come from a quite different technical background and 2) if your project involves other techniques as well.
If you find yourself wanting to learn electrophysiology, whether you are a student or a postdoc (or an adventurous PI!), here are a few tips from a very rookie postdoc to make the learning curve a bit smoother.
Set an objective
At the beginning you will need to learn the basics like preparing your slices/cells correctly, finding the pipette under the scope, sealing, breaking in a cell. My advice is to keep learning with a specific objective or biological question to answer. Not only will it keep you motivated, but also you may be able to generate some data, even if preliminary!
Know your tools
Spend time knowing what you use, including the different parts of the rig. This will give you a broader understanding of the technique and will allow you to troubleshoot efficiently when things don’t go as planned.
Spend time choosing the right cell
Choosing the right cell will determine the success of your patch. Spend time going around your prep, checking at different depths. If I’m in doubt I don’t patch and I keep searching for better one. Unsuccessful patch brings no data (or bad quality data), and it can turn a good day into a frustrating experience.
Complete integrated solution for patching cultured cells
Know when to call it a day
If the most basic things (e.g. sealing, rupturing…) are failing, and you have tried everything to troubleshoot, it is time to leave it. Take your time to identify what did not work out and come back the day after with the issue solved and a fresh mind.
Ask for help
I hope one day to fully learn the technique and become an expert, but that does not happen right away. If things get difficult, do not be afraid of asking someone who knows better. Most of the time you will see that even the most experienced people go through similar issues!
Something that is potentially very useful for starters is the creation of an electrophysiology club with other patch clampers in your institute. We have recently launched our own and the first meeting was very promising.
Don't be afraid to ask for help and also share your knowledge
Enjoy!
Electrophysiology is a very rewarding technique when things work out: you are seeing the electrical behaviour of a cell under your eyes!
Further reading
To finish this post, here are a few open access reviews that can get you started on the most fundamental theoretical aspects of patch-clamp electrophysiology:
- Kornreich B. G. (2007). The patch clamp technique: principles and technical considerations. Journal of veterinary cardiology: the official journal of the European Society of Veterinary Cardiology, 9(1), 25–37. https://doi.org/10.1016/j.jvc....
- Noguchi, A., Ikegaya, Y., & Matsumoto, N. (2021). In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives. Sensors (Basel, Switzerland), 21(4), 1448. https://doi.org/10.3390/s21041...
- Linders, L. E., Supiot, L. F., Du, W., D'Angelo, R., Adan, R., Riga, D., & Meye, F. J. (2022). Studying Synaptic Connectivity and Strength with Optogenetics and Patch-Clamp Electrophysiology. International journal of molecular sciences, 23(19), 11612. https://doi.org/10.3390/ijms23...
- Bébarová M. (2012). Advances in patch clamp technique: towards higher quality and quantity. General physiology and biophysics, 31(2), 131–140. https://doi.org/10.4149/gpb_20...
About the author
Ana Dorrego-Rivas got her PhD in Neuroscience from the University of Bordeaux, France. She is currently a postdoc at the Centre for Developmental Neurobiology (King's College London) investigating structural and functional heterogeneity in dopaminergic neurons of the olfactory bulb.
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