Potential Shifts and Intracellular Signaling in Smooth Muscle and Exocrine Cells: Role of the Secretory Potential (a Working Hypothesis)

Abstract

1 Franko National University, Lviv, Ukraine. Correspondence should be addressed to V. V. Manko (e-mail: vvmanko@franko.lviv.ua). Due to certain reasons, results of electrophysiological studies of secretory cells of the exocrine glands have until now been interpreted to a great extent within the framework of concepts proposed for excitatory cells and, especially, for smooth muscle cells. The statement that “... changes in the functioning of the cell are based on changes of its membrane potential” was transferred from physiology of the excitatory cells to physiology of the secretory cells. Indeed, there are some clear analogies between electrophysiological processes and their structural basis in secretory cells of the exocrine glands and smooth muscle cells. These are the relatively low values of the membrane potential, the existence of close cell-to-cell contacts, the presence of a certain set of Ca transport systems, the absence of an endoplasmic reticulum characterized by a sufficiently perfect structure (as in the case of skeletal muscle cells), and, as a consequence, the significant role of extracellular Ca in the coupling of the membrane and intracellular processes. Probably, these features are related not to a common origin of the above cell types but to slow temporal characteristics of the functions performed by these cells. These similarities allowed investigators to transfer interpretations of the experimental data obtained on smooth muscles onto secretory cells, which obviously promoted studies of the latter units. Nonetheless, direct applications of such an approach began to hinder to a certain extent electrophysiological studies of exocrine cells. Obvious discrepancies became clear when it was necessary to correlate directions of changes of the membrane potential of these cells with their secretory activity. It is well known that exocrine secretory cells differ from smooth muscle cells in their inability to generate action potentials, and only the so-called secretory potential is recorded from these cells after the action of a primary messenger. The use of modern microcytofluorometry techniques showed that the natural functional activities of smooth muscle and exocrine cells are initiated according to fundamentally different schemes. In the former case, this is such a chain: action of the primary messenger → shift of the membrane potential → activation of Ca channels of the plasma membrane and/or intracellular stores → an increase in the level of cytosol Ca → changes in the functional activity (contraction). In other words, changes in the membrane potential in this case are the reason for changes in the latter activity. At the same time, in the secretory cells changes in their membrane potential are not a reason for but a result of the processes realized within the cell; the chain of events is as follows: action of the primary messenger → activation of intracellular Ca channels → increase in the cytosol Ca concentration → activation of Ca-sensing channels → change in the membrane potential. In this scheme, the importance of changes in the membrane potential remains unclear: Why should it be changed when the secretion process has already been activated? We hypothesize that the secretory potential can: (i) modify the Ca signal indirectly, via Ca transport systems of the plasma membrane and, in such a way, influence the secretion, and/or (ii) directly limit or promote certain stages of exocytosis. Both these assumptions can be considered only working hypotheses. It is probable that they are both wrong. Nonetheless, the secretory potential performs some function, and if we take this into consideration, we shall be able to better interpret the variability of secretory potentials recorded from different exocrine cells.