Stimulation of secretory cells with muscarinic agonists leads to an increase in the intracellular Ca2+ concentration ([Ca2+]i), which activates protein secretion through exocytosis and causes closure of gap junctions between adjacent cells. In addition, the increase in [Ca2+]i activates three different kinds of ion channels: large K+ channels, Cl- channels and non-specific cation channels. The opening of those channels leads to an increase of [Na+] and a decrease of [Cl-] and [K+] in the cell. The two components that contribute to the increase in [Ca2+]i are calcium release from intracellular stores, localised in the endoplasmic reticulum and calcium influx through the plasma membrane. Several models for the regulation of [Ca2+]i have been proposed, including a recently suggested model whereby a distinct pathway involving arachidonic acid is added to the well-established capacitative model. Different hypotheses concerning coupling between the intra-cellular calcium stores and membrane channels co-exist. In addition to a historical overview, recent developments and future challenges are discussed in this review.
- Calcium signalling
- Muscarinic agonists
- Inositol 1, 4, 5-triphosphate
- Capacitive model