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.