What Does Physiological Mean?

S © t a r ecentl y r e vie wed an original paper with a title including he words “physiological stimulation.” In this particular case, t turned out that the stim ulation w as far fr om physiological. he concentration of the hormone used for acti v ation w as w ay bov e the maximal level ever observed in vivo, and this made e think about the use, and misuse, of the word “physiologial.” It is a word that we (physiologists) employ fr equentl y and erhaps too fr equentl y. Papers in physiological, and other, jourals often refer to “physiological conditions,” which sometimes s taken to indicate experiments in vi v o, but also fr equentl y ust means that experiments on single cells or tissue fragents were carried out with stimulation protocols and under ircumstances that are not unlike those that could happen n vi v o. We hav e li v ed thr ough a long and pr oducti v e period of singleell biology. Very important discoveries of real significance have een made, but it is now becoming incr easingl y clear that ther e r e many criticall y important inter actions betw een different djacent cell types in most tissues. To c har acterize these proesses, it is necessary to observe simultaneously more than one ell type in individual organs or tissues. Furthermore, the behavor of a particular cell type in isolation may not be the same as hen it is embedded in its normal environment. Of particular oncern is the tacit assumption in many studies that processes n cell lines reflect those in normal cells in situ. It may therefore e useful to reflect on the usefulness of working under real physological conditions, notwithstanding the obvious difficulties of oing so. In what follows, I’ll try to illuminate these issues by xamples from immunology, epithelial physiology, and neurocience. Ca 2 + signaling studies in imm une cells hav e been immensel y uccessful in unravelling key Ca 2 + transport events and, in articular, the properties of the Ca 2 + r elease acti v ated Ca 2 + CRAC) channel of the Orai type and its molecular control echanism. 1 Unlike the situation in epithelial cells, where Ca 2 +