Adrenomedullin influences dissociated rat area postrema neurons

The area postrema (AP) is one of a specialized group of central nervous system (CNS) structures devoid of a significant blood-brain barrier (BBB), collectively known as the circumventricular organs (CVO). While peptides are normally excluded from access to most regions of the CNS, the AP contains neurons with a high density of receptors for many circulating peptides, very likely including those for adrenomedullin (AM). In this study, whole-cell patch-clamp recordings were obtained from 114 dissociated rat AP neurons. The mean resting membrane potential (RMP) of these neurons (n=79) was -54.3+/-0.8 mV, the mean input resistance (IR) was 3.1+/-0.2 GOmega and the spike amplitude of neurons included in this study was always greater than 90 mV. Current-clamp studies showed that bath application of AM depolarized 39.2% (31 of 79) and hyperpolarized 45.6% (36 of 79) of neurons tested. Both effects were found to be concentration dependent from 10(-12) to 10(-7) M. These data support the idea that specific populations of CNS neurons within the AP are directly influenced by AM and support the concept that AM may act at AP to influence central autonomic control. We also examined the roles of specific ion channels in regulating the AM-induced excitability of AP neurons through voltage-clamp studies. These experiments suggest potential actions of AM in modulating voltage gated calcium channels, effects which have the additional consequence of inhibiting calcium activated potassium conductances (I(K(Ca))). These data demonstrate direct effects of AM on dissociated AP neurons and identify ion channels, the modulation of which, may underlie these effects.