Modulation of acetylcholine receptor channel kinetics by hydrocortisone

The kinetics of the nicotinic acetylcholine receptor (AChR) channel were analysed in the presence of hydrocortisone (HC, 100-400 μM), an electrically neutral steroid. The channel open time decreased, and in contrast to control conditions did not show any voltage dependency. However, HC induced a new (blocked) component in the closed time distribution, with a time constant that decreased with membrane hyperpolarization. HC decreased also, in a concentration-dependent way, the open time per burst. After coupling HC to bovine serum albumin, to restrict the place of steroid action at the external surface of the membrane, a voltage dependency of steroid action persisted. The effects of HC on the open and blocked time constants did not depend on agonist concentration, but was dependent on the type of agonist used (acetylcholine or nicotine). These results support the hypothesis that HC molecules bind near the agonist binding site.