Abstract
Despite the fact that paraventricular nucleus (PVN) neurones innervating the rostral ventrolateral medulla (RVLM) play important roles in the control of sympathetic function both in physiological and pathological conditions, the precise mechanisms controlling their activity are still incompletely understood. In the present study, we evaluated whether the transient outward potassium current I(A) is expressed in PVN-RVLM neurones, characterized its biophysical and pharmacological properties, and determined its role in shaping action potentials and firing discharge in these neurones. Patch-clamp recordings obtained from retrogradely labelled, PVN-RVLM neurones indicate that a 4-AP sensitive, TEA insensitive current, with biophysical properties consistent with I(A), is present in these neurones. Pharmacological blockade of I(A) depolarized resting V(m) and prolonged Na(+) action potential duration, by increasing its width and by slowing down its decay time course. Interestingly, blockade of I(A) either increased or decreased the firing activity of PVN-RVLM neurones, supporting the presence of subsets of PVN-RVLM neurones differentially modulated by I(A). In all cases, the effects of I(A) on firing activity were prevented by a broad spectrum Ca(2+) channel blocker. Immunohistochemical studies suggest that I(A) in PVN-RVLM neurons is mediated by Kv1.4 and/or Kv4.3 channel subunits. Overall, our results demonstrate the presence of I(A) in PVN-RVLM neurones, which actively modulates their action potential waveform and firing activity. These studies support I(A) as an important intrinsic mechanism controlling neuronal excitability in this central presympathetic neuronal population.