Calcium stimulus-response coupling

Cellular Calcium Regulation Calciiun plays critical roles in cellular communication and regulation. The normally very low resting free ionized concentration of Ca is maintained by a variety of ion channels, pumps, and intracellular storage processes. The elevation of intracellular Ca levels during cell stimulation serves to couple information with cellular response -stimulus-response coupling. The control of Ca " homeostasis represents, therefore, a potentially powerful control of cellular excitability and response [ 5 ]. 

Stimulus Response Coupling, the Role of Intracellular Calcium-binding Proteins, V. L. Smith, J. R. Dedman, eds. CRC Press, Boca Raton, FL 1990. 

THE POSSIBLE INVOLVEMENT OF PHOSPHATIDYLINOSITOL BREAKDOWN IN THE MECHANISM OF STIMULUS-RESPONSE COUPLING AT RECEPTORS WHICH CONTROL CELL-SURFACE CALCIUM GATES... 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

Clearly, the most studied aspect of stimulus-secretion coupling is the requirement for calcium. That Ca ions are essential for many cellular processes has been known since the days of Sidney Ringer [178], The eloquent studies of Douglas and his collaborators [179, 180] and others [181] firmly established the necessity for Ca in exocytotic secretion and set forth the notion that an increase in the level of free intracellular Ca, [Ca2+]j was responsible for initiating exocytosis. Evidence for increases in the level of intracellular free Ca as prerequisite for initiating exocytosis by cell surface stimulation is now available from studies using a variety of systems [181-183]. 

Secretion is the opposite process to that of absorption. In response to various stimuli, crypt cells actively transport chloride into the gut lumen and sodium and water follow. This stimulus-secretion coupling is modulated by cyclic AMP and GMP, calcium, prostaglandins and leukotrienes. 

During activation of postganglionic sympathetic nerves there is an exocytotlc release of norepinephrine which is dependent upon the movement of calcium across the neural cell membrane. The effects of CEB on stimulus-secretion coupling in S3nnpathetlc nerves has been studied in several different preparations. Verapamil does not affect the neural release of norepinephrine in either Isolated cat heart or in the pithed rat. In the latter model nifedipine blunted increases in blood pressure due to activation of sympathetic nerves but did not affect cardiovascular responses to exogenous norepinephrine suggesting a prejunctional site of inhibition. 

As pointed out by Rasmussen [201, 203] the stimulation of cyclic AMP is unidirectional. We know how it is produced, but we do not know how it is turned off after the cell response. We have seen many examples in which the ultimate product of a biological stimulus is inhibited by the initial stimulus thus closing what is called a feedback loop (see Inborn Errors— Hormones). Rasmussen believes that if the actions of calcium and cAMP are coupled, such a feedback loop can be achieved. Calcium concentrations in the extracellular fluid, the cytosol and the mitochondria are 10", 10" 10" molar respectively, thus the calcium... 

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