Altered A‐type potassium currents (IA) in RVLM‐projecting PVN neurons during hypertension

Accumulating evidence indicates that RVLM‐projecting PVN neurons (PVN‐RVLM) regulate sympathetic outflow, and that enhanced activity in this pathway contributes to sympathoexcitation during hypertension. Still, the mechanisms leading to over‐activity in this pathway during hypertension remain unknown. The goal of this study was to determine whether changes in the biophysical properties of the transient K+ current, IA, results in increased neuronal excitability in PVN‐RVLM neurons during hypertension. Patch clamp recordings were obtained from PVN‐RVLM neurons in 2‐kidney, 1‐clip hypertensive rats. During hypertension, a diminished IA peak amplitude (P<0.0001), as well as a depolarizing shift in the voltage‐dependence of activation (P<0.001) were found. Moreover, a hyperpolarizing shift in the voltage‐dependence of inactivation of IA (P<0.0001), along with a diminished rate of recovery from inactivation (P<0.0001), were observed during hypertension. No changes in other IA properties (including activation/inactivation kinetics, among others) were observed. Overall, these data support a diminished IA availability in PVN‐RVLM neurons during hypertension. Finally, the basal firing rate of PVN‐RVLM neurons (in the presence of synaptic blockers) was ~53% higher during hypertension. Previous work from our lab demonstrated that IA restrains ongoing firing activity in these neurons. Thus, current experiments aim at addressing the contribution of diminished IA availability to increased PVN‐RVLM excitability during hypertension. Supported by NIH RO1 HL68725 (JES).