Functional role of A-type potassium currents in rat presympathetic PVN neurones

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 Ca²⁺ 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_Ain 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.