Effects of Cl- substitution on electrophysiological properties, Ca2+ influx and prolactin secretion of rat lactotropes in vitro

In this study, we compared the effects of different chloride (Cl-) substitutes - methane sulfonate (CH3SO3-), bromide (Br-), nitrate (NO3-), thiocyanate (SCN-) and perchlorate (ClO4-)- on the secretory activity and calcium current activation of rat lactotropes in primary culture. We observed that CH3SO3- decreased basal prolactin (PRL) secretion. Br- had no effect, whereas the more lyotropic anions, such as NO3-, SCN- and ClO4-, increased basal PRL secretion. The latter three substitutes induced a significant shift in the voltage dependence of T-type calcium channel activation towards hyperpolarized values. However, this shift alone cannot explain the increase in secretion. Anion permeability studies also demonstrated that the organic anion CH3SO3- was less permeant than Cl-, whereas monovalent inorganic anions were more permeant, with the following anion permeability sequence: SCN->ClO4->NO3->Br-. In conclusion, deprivation of Cl- ions has converse consequences on basal and induced secretion; permeating anions result in a transient increase in intracellular Ca2+ ions. This process involves voltage dependent Ca2+ channels. We propose that an alteration in intracellular anion concentrations may influence the activation of internal effecters such as G proteins or channel proteins and, therefore, interfere with exocytosis. These effects a re correlated with an external action of lyotropic anions, particularly NO3-, ClO4- and SCN-, on the gating properties of T-type calcium channels, probably through changes in cell surface charges. The results demonstrate the modulatory effect of anions on the secretory activity of rat lactotropes and underline the specific role played by chloride in stimulus-secretion coupling. Copyright (C) 1999 S. Karger AG, Basel.