Potentiation of K+-evoked catecholamine release in the cat adrenal gland treated with ouabain.

1 A vigorous catecholamine secretory response was evoked by small increments (2-10 mM) of the extracellular concentration of K+ ([K+])o) in cat adrenal glands treated with ouabain (10(-4) M), and perfused with Krebs-bicarbonate solution at room temperature. 2 The secretory response depends on [K+]o; increments of [K+]o as small as 2 mM for 2 min evoked a clear secretory response; at 10-17.7 mM K+, the maximal secretory response was observed. In normal glands, not treated with ouabain, no increase of the rate of catecholamine output was observed by raising [K+]o up to 17.7 mM for 2 min. 3 The K+ secretory response was time-dependent, requiring at least 1 min to be initiated; on continued exposure to 10 mM [K+]o, the enhanced response remained for at least 1 h. 4 In low [Na+]o, the K+-secretory response was unchanged. However, in 0-Ca2+, high-Mg2+ solutions, or in the presence of D600, an organic Ca2+ antagonist, it was abolished. 5 The K+-induced secretory response was not altered in the presence of tetrodoxin or tetraethylammonium. 6 It is concluded that ouabain potentiated the catecholamine secretory response to raised [K+]o by increasing the amount of Ca2+ available to the secretory machinery through (a) mobilization of an enhanced pool of membrane-bound Ca2+, (b) activation of membrane Ca2+ inward current; or (c) decrease of intracellular Ca2+ buffering systems. The activation by ouabain of a membrane Na+-Ca2+ exchange system is not involved in this K+-secretory response. It is suggested that the plasma membrane ATPase enzyme system, by changing the affinity of its Ca2+ binding sites, might control the availability of this cation to the secretory machinery and, therefore, modulate catecholamine secretion in the adrenal gland.