Large conductance Ca2+-activated K+ (BK) channels promote secretagogue-induced transition from spiking to bursting in murine anterior pituitary corticotrophs

摘要

Key points Corticotroph cells of the anterior pituitary are electrically excitable and are an integral component of the hypothalamic-pituitary-adrenal axis which governs the neuroendocrine response to stress. Corticotrophs display predominantly single spike activity under basal conditions that transition to complex bursting behaviours upon stimulation by the hypothalamic secretagogues corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP); however, the underlying mechanisms controlling bursting are unknown. In this study, we show that CRH and AVP induce different patterns of corticotroph electrical activity, and we use an electrophysiological approach combined with mathematical modelling to show the ionic mechanisms for these differential effects. The data reveal that secretagogue-induced bursting is dependent on large conductance Ca2+-activated K+ (BK) channels and is driven primarily by CRH whereas AVP promotes an increase in single-spike frequency through BK-independent pathways involving activation of non-selective cation conductances. As corticotroph excitability is differentially regulated by CRH and AVP this may allow corticotrophs to respond appropriately to different stressors.