Properties of the calcium signal in ocular cell types. Transient receptor potential channels: Relevant for the clinic?

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ECTS and Course type

ECTS: 2

Course type:Lecture/seminar

Target audience

All fellows/students (MSc, PhD) interested in Ca2+ signaling and TRP channel research

Date and time

From January to March (if weekly scheduled) (6 weeks, e.g. from 4:00 pm).

Location

Library in the Dept. of Ophthalmology, CVK (library); Location can be changed dependent on the number of participating students.

Learning outcome

Calcium is the most universal carrier of biological signals. It modulates cell life from its origin at fertilization to its end in the apoptotic process. Cells need Ca2+ to correctly carry out most of their important functions. At this point, Ca2+ permeable transient receptor potential channels (TRPs) play a crucial role in cellular signaling in all kind of excitable cells. They also play a role in non-excitable (ocular) cells and (ocular) tumor cells.
The participants of the course will acquire knowledge about experimental ophthalmology with clinical aspects using high sensitive functional assays such as fluorescence calcium imaging and (planar) patch-clamping. Videos of these methods will be shown. More specifically, students will learn the function of Ca2+ binding proteins, Ca2+ homeostasis, regulation of intracellular Ca2+ compartmentalization, Ca2+ channels and pumps, identification and function of TRPs (e.g. Ca2+ signal and cell proliferation in context with TRPs). Furthermore, students will be able to understand some relevant contributions of the TRPs and their typical characteristics in context with ocular (tumor) diseases (e.g. dry eye syndrome, pterygium, uveal melanoma). Moreover, the students will understand how certain TRPs can be identified and the relevance of the aforementioned methods in electrophysiology. Finally, the students will learn how to transfer this knowledge to interdisciplinary topics between medical neurosciences and experimental ophthalmology.

Structure

The lecture may be assigned to the following weekly subunits
(e.g. always 15-20 min presentation and 10 min active discussion of the students):

  1. History and evolution of calcium biochemistry
  2. Ca2+ homeostasis, channels and pumps
  3. TRP channels and methods for their electrophysiological detection
  4. TRP channels on the eye surface: Relevant for the clinic?
  5. Experimental ophthalmology and daily clinic
  6. Scientific practice in electrophysiology, lab tour if required

The journal club will be scheduled after the lecture (ca. 40 min presentations and discussions)

Assignments/Exam

Short and long essay questions about the content of the lecture can be prepared for grading if applicable.
Presentations for Journal Club is scheduled

Readings

Mandatory:

  • B. Nilius and G. Owsianik. Transient receptor potential channelopathies. Pflugers Arch 460 (2):437-450, 2010.
  • S. Mergler and U. Pleyer. The human corneal endothelium: New insights into electrophysiology and ion channels. Prog.Retin.Eye Res. 26 (4):359-378, 2007.
  • Mergler, S., Reinach P.S., et al. (2014). "Temperature-sensitive transient receptor potential channels in corneal tissue layers and cells." Ophthalmic Res 52(3): 151-159.
  • Reinach, P. S., Mergler S., et al. (2015). "Polymodal roles of transient receptor potential channels in the control of ocular function." Eye Vis (Lond) 2(1): 5.
  • Reinach, P. S., Mergler S., et al. (2016). "Ocular transient receptor potential channel function in health and disease." BMC Ophthalmology BMC Ophthalmol 15 Suppl 1: 153.
  • Khajavi, N., Mergler S., et al. (2017). "3-Iodothyronamine, a Novel Endogenous Modulator of Transient Receptor Potential Melastatin 8?" Front Endocrinol (Lausanne) 8: 198.

Further:

  • Pamir, E., et al. (2008). "Planar patch-clamp force microscopy on living cells." Ultramicroscopy 108(6): 552-557.
  • A. Bruggemann, S. Stoelzle, M. George, J. C. Behrends, and N. Fertig. Microchip technology for automated and parallel patch-clamp recording. Small 2 (7):840-846, 2006.
  • Milligan, C. J., et al. (2009). "Robotic multiwell planar patch-clamp for native and primary mammalian cells." Nature Protocols 4(2): 244-255.


Original papers (some suggestions):

  • S. Mergler, M. Skrzypski, M. Sassek, P. Pietrzak, C. Pucci, B. Wiedenmann, and M. Z. Strowski. Thermo-sensitive transient receptor potential vanilloid channel-1 regulates intracellular calcium and triggers chromogranin A secretion in pancreatic neuroendocrine BON-1 tumor cells. Cell Signal. 24 (1):233-246, 2012.
  • S. Mergler, C. Mertens, M. Valtink, P. S. Reinach, V. C. Szekely, N. Slavi, F. Garreis, S. Abdelmessih, E. Turker, G. Fels, and U. Pleyer. Functional significance of thermosensitive transient receptor potential melastatin channel 8 (TRPM8) expression in immortalized human corneal endothelial cells. Exp Eye Res 116:337-349, 2013.
  • S. Mergler, R. Derckx, P. S. Reinach, F. Garreis, A. Bohm, L. Schmelzer, S. Skosyrski, N. Ramesh, S. Abdelmessih, O. K. Polat, N. Khajavi, and A. I. Riechardt. Calcium regulation by temperature-sensitive transient receptor potential channels in human uveal melanoma cells. Cell Signal. 26 (1):56-69, 2013.
  • Khajavi, N., Mergler, S., et al. (2014). "L-Carnitine Reduces in Human Conjunctival Epithelial Cells Hypertonic-Induced Shrinkage through Interacting with TRPV1 Channels." Cell Physiol Biochem. 34(3): 790-803.
  • Khajavi, N., Mergler, S., et al. (2015). "Thyronamine induces TRPM8 channel activation in human conjunctival epithelial cells." Cell Signal 27(2): 315-325.
  • Lucius, A., Mergler, S., et al. (2015). "3-Iodothyronamine increases transient receptor potential melastatin channel 8 (TRPM8) activity in immortalized human corneal epithelial cells." Cell Signal 28(3): 136-147.
  • Garreis, F., Mergler, S. et al. (2016). "Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+ Influx Dysfunction in Human Pterygial Cells." Invest Ophthalmol Vis Sci 57(6): 2564-2577.