Effects of extracellular potassium and 4-aminopyridine on corticosteroid secretion

Transient alteration in [K+]0 significantly influenced basal and stimulated corticosteroid secretory activity of superfused rat adrenal cortical tissue slices. A transient rise in [K%]0 resulted in an increase in basal steroid secretion. Removal of extracellular K+ from the superfusing medium significantly reduced basal as well as ACTh and cAMP-stimulated steroid production. Elevated [K+0] significantly potentiated cAMP's and to a much lesser extent increased ACTH's steroid stimulatory activity. The K+ flux inhibitor, 4-aminopyridine (4AP) (10 mM) elicited an initial decline in basal steroid secretory activity. A single 10-ml dose of 10 mM but not 1 mM 4AP significantly diminished, for many hours, ACTH's and cAMP's ability to stimulate adrenal steroid secretion. The combination of elevated [K+]0 and 4AP administration resulted in additional reduction of the ability of ACTH to stimulate steroid production. This combination of 4AP with [K+]0 elevations also blocked the potentiating effect of K+ on cAMP-stimulated steroid secretion. Together these findings demonstrated that some procedures which can alter the distribution of K+ across the adrenal cell membrane are capable of profoundly influencing the secretion of the predominant glucocorticoid from the rat adrenal gland under in vitro superfusion conditions. The data support the suggestion that a slight rise in intracellular K+ concentration would be stimulatory and that further increase of, or a decline in, this ion's intracellular level would be inhibitory to basal and stimulated steroid secretory activity.