Selective Enhancement of an A Type Potassium Current by Dexamethasone in a Corticotroph Cell Line

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Abstract
Perforated patch recording was used to examine the effect of the synthetic steroid dexamethasone on the whole cell potassium (K+) current, in the mouse corticotroph tumour cell line AtT20/D16‐16. In 15 out of 52 control cells (29%) there was a rapidly‐activating, rapidly‐ inactivating K+ current of the A type, the amplitude of which was strongly dependent on the holding potential in use prior to its activation by depolarising voltage pulses, and which was blocked by 1 mM 4‐aminopyridine (4‐AP, n = 5). The effect of dexamethasone (100nM, 2h, 37°C) was that the A current increased in prevelance (24 out of 31 cells, 77%), lost its dependence on holding potential (over the range studied), and as a result became significantly larger than in controls, for certain voltage steps (peak A current density was 18.5 +2.4 pA/pF (n = 12) for control cells and 26.3 ± 3.9 pA/pF (n = 18) for dexamethasone treated cells, for a step to +30mV from ‐60mV, values are mean ± SEM). All cells exhibited a slowly‐activating, sustained K+ current, which was unaffected by changes in the holding potential, unaffected by 4‐AP and consisted of at least 3 components: one blocked by 30 mM tetraethylammonium(TEA) or 100 nM charybdotoxin (CTX); a second blocked by 100 nM apamin; and a third not blocked by TEA, CTX, apamin, clofilium (100 nM) or niflumic acid (0.1 mM). Dexamethasone produced no change in the slowly‐activating, sustained current nor in any of its individual components. The effect of dexamethasone on the A current was completely blocked by 0.1 mM puromycin, a protein synthesis blocker, while puromycin alone did not affect the size or frequency of the A current, nor alter the slowly‐activating, sustained current. Secretion studies using 4‐AP confirmed that the A current has a role in stimulated adrenocorticotrophic hormone (ACTH) secretion. In summary, AtT20 cells contain at least four types of K+ current: an A current and 3 currents contributing to the slowly‐activating current. Selective enhancement of the A current by dexamethasone, shown here to require synthesis of new protein, is one of the mechanisms whereby glucocorticoids exert inhibitory control on ACTH secretion.

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