On Depolarization-Evoked Exocytosis as a Function of Calcium Entry: Possibilities and Pitfalls

Secretion from many endocrine cells is a result of calcium-regulated exocytosis due to Ca2+ influx. Using the patch-clamp technique, voltage pulses can be applied to the cells to open Ca2+ channels, resulting in a measurable Ca2+ current, and evoke exocytosis, which can be seen as an increase in membrane capacitance. A common tool for evaluating the relation between Ca2+ influx and exocytosis is to plot the increase in capacitance (ΔC(m)) as a function of the integral of the measured Ca2+current (Q). When depolarizations of different lengths are imposed, the rate of exocytosis is typically higher for shorter than for longer pulses, which has been suggested to result from depletion of a granule pool or from Ca2+ current inactivation. It is here demonstrated that ΔC(m) as a function of Q can reveal whether Ca2+ current inactivation masquerades as pool depletion. Moreover, it is shown that a convex, cooperativity-like, relation between ΔC(m) and Q surprisingly cannot occur as a result of cooperative effects, but can result from delays in the exocytotic process or in Ca2+dynamics. An overview of expected ΔC(m)-versus-Q relations for a range of explicit situations is given, which should help in the interpretation of data of depolarization-evoked exocytosis in endocrine cells