The discovery of the Interstitial Cells of Cajal as pacemakers of the gastro-intestinal system originated by research of Dr Lars Thuneberg, Panum Institute, Copenhagen University. Dr Thuneberg had developed very gently forms of fixation for electron microscopy that allowed him to see very fine details about the interaction between smooth muscle cells, interstitial cells of Cajal and Enteric neurons.
This lead to a paper in 1982 with the title “Interstitial cells of Cajal: intestinal pacemaker cells?”
During my Ph.D. studies I had frequently meetings with Lars Thuneberg about problems I had with getting micro-electrodes into the enteric neurones of the pig small intestine. A matter he actually had adressed and he suggested that the problem was due to high amounts of collagen in the pig intestine and I probably should use newborn pigs instead because there would be much less collagen. That worked and I manage to publish a full characterization of the neurones of the pig enteric nervous system in Journal of Physiology in 1997.
During our meetings Thuneberg who was an anatomist had counter questions he wanted to know if the “peg-and socket” junctions he could identify by EM could be involved in any form for electrical signalling. I did suggest that due to the large area of contact there might be a capacitive coupling between the smooth muscle cells and the interstitial cells of Cajal and in that way mediate electrical signalling between the cells.
We found it so interesting that we wrote an application to the Carlsberg Foundation for a stay at McMaster University where Thuneberg had a collaboration with Prof Jan Huizinga.
To make the story short it ended with a paper in 1998 in Nature Medicine which was hailed as a milestone in gastrointestinal research and a publication that was settling the 15 year old question Thunberg had asked in 1982
The publication is has been cited more than 390 times and been foundation for research into creating artificial pacemakers of the gut and it has been demonstrated that gastrointestinal stromal tumors (GIST’s) probably arise from this cell type.