INTRACELLULAR CA2-CELLS( SIGNALING IN SECRETORY)

The secretion of ions and fluid plays a critical role in a variety of physiological activities that are vital to mechanisms in animals, Cont rol of such activity is achieved by a range of neurotransmitters and h ormones many of which act intracellularly by generating the second mes senger inositol 1,4,5-trisphosphate (InsP(3)) and increasing cytosolic free calcium ion concentrations ([Ca2+](i)). These increases are achi eved by a combination of the InsP(3)-induced release of Ca2+ from spec ific intracellular stores and the activation of Ca2+ entry from the ex tracellular environment, The [Ca2+](i) signal represents a balance bet ween the adequate activation of components of the secretory mechanism and the avoidance of [Ca2+](i) levels that are toxic to the cell. Rest ing [Ca2+](i) is maintained low by the action of Ca2+ pumps on the int racellular stores and plasma membrane, with the result that gradients for Ca2+ movement into the cytosol from either of these two sources ar e very large and there is considerable potential for achieving rapid i ncreases in [Ca2+](i). Consequently, for successful Ca2+ signalling, i t is imperative that these two mechanisms of raising [Ca2+](i) (i.e. C a2+ release and Ca2+ entry) are closely integrated, Current models emp hasize the activation of Ca2+ entry as a downstream result of the empt ying of the intracellular stores ('capacitative' model), Whilst this m ay be true for situations of maximal stimulation, recent experiments o n the oscillatory [Ca2+](i) responses typical of more physiological le vels of stimulation indicate a previously unsuspected, independent act ivation of Ca2+ entry involving arachidonic acid. This arachidonic-aci d-activated entry plays a key role, along with InsP(3), in inducing th e repetitive release of Ca2+ from the stores to produce the [Ca2+](i) oscillations. In this way, the two components responsible for the elev ation of [Ca2+](i) are intimately related and their dual effects close ly coordinated, resulting in the finely tuned control of agonist-induc ed changes in [Ca2+](i).