Corticotroph cells from the anterior pituitary are an important component of the hypothalamic-pituitary-adrenal (HPA) axis, which controls the neuroendocrine response to stress. HPA axis dysfunction can have many consequences on health. In response to a stressor, the hypothalamic neuropeptides corticotrophin-releasing hormone (CRH) and AVP stimulate ACTH release from corticotrophs. ACTH, in turn, releases glucocorticoids (corticosterone in rodents) from the adrenal gland which negatively feedback to inhibit ACTH secretion. Corticotroph cells are electrically excitable and fire single-spike action potentials as well as showing complex bursting patterns. The aim of this project was to establish whether glucocorticoid negative feedback changes the electrical properties of murine corticotroph cells. Corticotrophs were cultured from male mice (aged 2-5 months) constitutively expressing GFP under control of the POMC promoter (POMC-GFP). Electrophysiological recordings were obtained using the perforated patch clamp technique in the current clamp configuration. Under basal conditions, cells had a resting membrane potential of -53.7 ±1.5mV (n = 7, Data are Means ± SEM) and showed low frequency spontaneous action potentials (0.34 ±0.14Hz). CRH and AVP (0.2nM and 2nM respectively) caused a significant (p < 0.01, ANOVA) depolarisation of the resting membrane potential to -47.4 ±0.74mV. There was also a significant (p < 0.01) increase in firing frequency from 0.34 ±0.14Hz to 0.99 ±0.27Hz. The increase in firing frequency was associated with a transition from a predominantly single-spike firing pattern to a bursting-like behaviour. Cells pre-treated for 1.5 hours with corticosterone (100nM) were significantly (p < 0.01) hyperpolarised compared with controls (-62.9 ±2.2mV) under basal conditions (n = 8). Although CRH and AVP could depolarise resting membrane potential this was still significantly (p < 0.05) hyperpolarised (-55.7 ±2.6mV) compared with controls treated with CRH and AVP. Basal firing rate was lower in cells treated for 1.5 hours (0.12 ±0.1Hz) and although CRH/AVP was still able to increase firing frequency (0.49 ±0.13Hz), it was significantly (p < 0.05) reduced compared with control cells exposed to CRH and AVP. Furthermore, in corticosterone pre-treated cells, CRH and AVP failed to induce a significant transition from single spikes to bursting behaviour. These results demonstrate that physiological concentrations of CRH/AVP produce a robust membrane depolarisation and increase in firing frequency of murine corticotroph cells. Treatment with corticosterone causes an overall suppression of both spontaneous and CRH/AVP-evoked firing frequency. Thus glucocorticoid negative feedback involves modulation of the electrical excitability of native murine corticotrophs. The mechanisms and molecular targets for corticosterone action remain to be defined.