A Twenty-Year Trip through the Chromaffin Cell
ANTONIO G. GARCÍA
Instituto Teófilo Hernando, Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029, Madrid, Spain, and Servicio de Farmacología Clínica and Instituto de Gerontología, Hospital Universitario de la Princesa, Diego de León 62, 28006, Madrid, Spain
ABSTRACT: Described here is the origin of a fruitful, long-Iasting, and friendly international group of scientists whose main interests are chromaffin cells and exocytosis. Meetings have been held every two years in different countries of Europe and North America, and in Japan, Australia, and Israel. We have no formal society or written rules, and our intention is good science and friendship. The first of our International Symposia on Chromaffin Cell Biology (ISCCB-1) was held in Ibiza (Spain) in 1982, and the most recent (ISCCB-11) was held in San Diego (USA) in 2001. These symposia are attended by 100-150 scientists from most European countries, Japan, Israel, the United States, Canada, South America, and Australia. The interest in the chromaffin cell as a model for studying basic mechanisms of calcium signaling, cell-cell communication, exocytosis, and membrane and vesicle trafficking has been wide; I predict that this interest will grow in the coming years.
KEYWORDS: ISCCB; chromaffin cell; cell communication
The Pioneers of the ISCCB Meetings
The First ISCCB Meeting at Ibiza
A Twenty-Year Trip Through the ISCCB Meetings
The International Program Committee
The Future of the ISCCB meetings
Address for correspondence: Antonio G. García, Departamento de Farrnacología, Facultad de Medicina, Arzobispo Morcillo, 4, 28029, Madrid, Spain, Voice: +34-91-3975388; fax: +34-913975397.
In July 1981 a satellite meeting of the IUPHAR (International Union of Pharmacology) was organized by F. Izumi, K. Kumakura, J. Kurosawa, and M. Oka at the beautiful Hakone National Park in Japan. E. Costa, C. Gagnon, H.B. Pollard, M. Sandler, and O.H. Viveros helped to shape the program of this meeting, entitled "Synthesis, Storage and Secretion of Adrenal Catecholamine: Dynamic Integration of Functions." Sada Kirpekar was scheduled to deliver a talk in Hakone, but because of health problems, he asked me to deliver his talk. Thus, in Hakone I had my first contact with probably the first "independent" international meeting entirely devoted to the chromaffin cell. However, this interesting meeting seemed to be only an isolated experience, a mere satellite to IUPHAR; there appeared to be no opportunity for continued study in this area.
My next chromaffin cell experience occurred in Nottingham, England. The programs of the International Society of Neurochemistry (ISN) meetings often contained various symposia on biochemical aspects of the synthesis, storage, and metabolism of adrenal catecholamines, as well as on their exocytotic release from chromaffin cells. During the 1970s Bruce Livett contributed much to the development of techniques to isolate and culture the bovine adrenal medullary chromaffin cells. Every laboratory developed its own variations on the culture technique, and so I went for several weeks to the laboratory of Dominique Aunis to learn how to culture these cells. Dominique also visited my laboratory in Madrid, and subsequently we established a fruitful collaboration that lasted for several years in the 1970s and 1980s.
The possibility of culturing bovine chromaffin cells in unlimited amounts dramatically increased the interest in this model. Thus, at the ISN meeting held in Nottingham in September 1981, Bruce organized an ambitious roundtable entitled "The Chromaffin Cell as a Neurochemical Model". There were twelve speakers: B. Livett, O.H. Viveros, D.E. Knight, J.M. Trifaró, D. Aunis, S. Lemaire, K. Unsicker, A.G. García, H. Thoenen, G. Guroff, E. Fenwick, and E. Costa. When we arrived in Nottingham, we were too late to get any food in the student dormitories; Hans Winkler, Dominique Aunis, Humberto Viveros, Bruce Livett, Jose Maria Trifaró, and I decided to go downtown to get some dinner. After an intense search, we found only a pub open, and there we had snacks and beer. Probably because of the hypoglycemia/hyperalcoholemia that resulted, somebody (Winkler?) suggested that we organize a series of international meetings on chromaffin cells. The following day in the bus that took us to visit Chatsworth House, we discussed the program. I took notes on the suggestions for themes and speakers, and it was agreed that I would organize the first of these meetings in Spain. Hans Winkler, who likes the Alhambra, suggested Granada; later on, I thought that Ibiza, part of the Balearic Islands in the Mediterranean sea, would be more appropriate.
The Ibiza meeting received its baptism as "Molecular Neurobiology of Peripheral Catecholaminergic Systems," renamed ISCCB at Cool font. The first international program committee was formed: D. Aunis, A.G. García, M. Oka, J.H. Phillips, J.M. Trifaró, O.H. Viveros, E. W. Westhead, and H. Winkler. It was agreed that a speaker (25 minutes plus a 5-min discussion) would be invited for each major group working in the field and that the program should not be overloaded with too many scientific activities; 30 to 35 talks were scheduled during four days (Monday, Tuesday, Thursday, and Friday).
Extensive free time was given in order to see the posters, to favor the exchange of ideas, and to stimulate friendship and contact among people. Wednesday was free for a one-day excursion to the almost-wild island of Formentera, where we had a gigantic paella and a lot of fun. The summary of the meeting was presented by II scientists, each of whom, in five minutes, tried to predict the direction of future research on eleven topics: R. Levi-Montalcini, development and plasticity; N. Weiner, catecholamine synthesis; J.P. Henry, monoamine transporters; H. Winkler, chromaffin granules; B.G. Livett, comessengers; P. F. Baker, ions and exocytosis; L. Stjärne, receptors and exocytosis; J.J. Nordman, the exocytotic cycle; J.M. Trifaró, the cytoskeleton; H.B. Pollard, proteins of exocytosis; and W. de Potter, membrane fusion. We have been following the evolution of these topics and other additional topics through the subsequent ISCCB meetings.
TABLE 1. Locations of the International Symposia on Chromaffin Cell Biology
The ISCCB meetings have been held in various European (Spain, France, Germany, UK, Norway) and North American countries (USA, Canada), as well as in Australia, Israel, and Japan. It is interesting that a group of "chromaffinologists" is being developed by Ana Cárdenas in Valparaíso; we hope to extend our meetings and friends to several countries in Latin America in the near future.
TABLE 2. Members of the program committees for the 11 ISCCB meetings
Is there an ideal number of participants for these meetings? Personally, I think that 100 is an ideal number for accomplishing the objectives of Ibiza. However, 150 participants is quite good. Ricardo Borges intends to beat all records in La Palma in 2003, where he plans to recruit 200 scientists from all over the world.
TABLE 3 shows the distribution per country of the participants of the eight meetings for which I have information. It is curious that, after the United States, most participants came from Spain. This may be due to the fact that annual "parallel" meetings on chromaffin cells are held at various places in Spain. These meetings, which are traditionally held a few days before Christmas, have been attended more recently by scientists working in neurotransmission. For instance, the last meeting was held in December 2000 in Molina de Segura (Murcia) and was attended by loo neuroscientists. Other countries contributing regularly with 4-10 scientists have been the United Kingdom, Austria, Australia, Canada, France, Israel (particularly during the four initial meetings), and Norway, This, of course, is an indication of the presence in those countries of research groups with strong contributions to the field (see some of their leaders in TABLE 2, some of whom organized an ISCCB meeting).
TABLE 3. Number of participants in the 11 ISCCB meetings by country
TABLE 4. Questions posed in Ibiza 20 years ago with some answers
The chromaffin cell has the electrophysiological and secretory machinery necessary to trigger fast exocytosis in response to the activation of a cholinergic synapse. This cell also contains the machinery to synthesize and store catecholamines, and the membrane transport systems for various neurotransmitters and for the manufacturing and transport of dense-cored vesicles, from the Golgi apparatus to exocytotic subplasmalemmal active sites. Chromaffin cells express various subtypes of neuronal nicotinic receptor subunits, Na+ channels, various subtypes of K+ channels, Cl- channels, and up to four subtypes of high voltage-activated Ca2+ channels. Since the mouse adrenal chromaffin cell can now be readily cultured and knockout mice are available, I anticipate that this model will be widely used to study the role of many receptors, proteins, and ion channel subtypes in controlling the stimulus-secretion coupling process.
Concerning the handling of Ca2+, new Ca2+ sensors (aequorins, "ratiometricpericam") targeted to specific organelles (chromaffin vesicles, nucleus, mitochondria, cytosol, endoplasmic reticulum, and plasmalemma) will provide new knowledge on Ca2+ signals and Ca2+ redistribution following cell stimulation. These signals can now be correlated with the exocytosis of a few vesicles, measured with amperometric and capacitance techniques at the single-cell level. Particularly interesting will be the study of the oscillatory patterns of Ca2+ organelles derived from physiological stimuli, consisting of trains of action potentials.
In San Diego we saw a lot of studies on the regulation of specific genes expressing catecholamine-synthesizing enzymes, or on some of the proteins of the exocytotic machine. I am sure that the application of cDNA microarray techniques and bioinformatics will lead to an explosion of knowledge on how several hundreds of genes are overexpressed or underexpressed upon chromaffin cell stimulation. In this direction, Lee Eiden is already proposing to create a network to compute a model of the chromaffin cell.
I am optimistic about the future of the chromaffin cell field and about the ISCCB meetings. The chromaffin cells of various mammalian species will continue to be an excellent model for studying the basic electrophysiological and molecular mechanisms that trigger and maintain exocytosis. Exocytosis has the utmost biological relevance since it is the underlying basic mechanism of cell-cell communication in general, and between neurons in particular. This is a unique model that, in spite of much technical and methodological progress (who is capable of recording single- vesicle exocytosis at a mammalian CNS synapse?), will continue to be a basic research model for neurobiologists. I am sure that Ricardo Borges will manage to organize an excellent ISCCB-12 meeting and to recruit new and old chromaffin cell groups in 2003 in the beautiful island of La Palma. I look forward to seeing you there with new stimulating results and interesting ideas.
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