Potency of depolarization-induced transmitter release is determined by divalent cation influx in PC 12 cells

Evoked release of [³H]dopamine ([³H]DA) from pheochromocytoma cells (PC 12) is dependent on extracellular calcium ([Ca²⁺]_ex), but it ca place if calcium ions (Ca²⁺) are substituted by other divalent ions such as strontium (Sr²⁺) and barium (Ba²⁺). The potency of the divalent supporting release varies with the cell type; in PC 12 cells the order of potency is Ba²⁺>Sr²⁺>Ca²⁺. The close correlation Ca²⁺ entry and depolarization-evoked transmitter release prompted us to examine whether the higher evoked transmitter release in the presence of Sr su2+ correlates with an increased evoked Sr su2+ influx. Influx studies were conducted on PC12 cells using a radioactive tracer su45 Ca ⁸⁵Sr²⁺, <1μM) in the presence of either Sr²⁺ (0.5 mM) or Ca²⁺ (0.5 mM). Depolarization with KCl (60 mM) increased evoke when Ca²⁺ was substituted with Sr²⁺. Similarly, evoked ⁸⁵Sr²⁺ influx increased 1.87-fold by substituting Ca²⁺ for Sr²⁺. Thus th cation influx is determined by the type of divalent ion which is accessible in the extracellular medium, independently of the radioactive tracer used. Increased evoked transmitter release in the presence of Sr²⁺ was associated with increased evoked Sr²⁺ influx. This suggests that the potency o transmitter release is determined predominantly by the influx of divalent cations. Furthermore, the steps subsequent to cation influx in the release process are equally efficient for both cations.