Diminished Intracellular Calcium in the Hypothalamic Paraventricular Nucleus Augments Neuronal Excitability and Sympathetic Nerve Activity

We have demonstrated that hypertension induced by high salt diet combined with chronic low-dose infusion of angiotensin II (AngII-Salt HTN) involves dysfunction of small conductance calcium-activated potassium (SK) channels in the hypothalamic paraventricular nucleus (PVN). Diminished current conducted through SK channels augments neuronal excitability, and inhibition of SK channel function in the PVN augments sympathetic outflow and arterial blood pressure (ABP); however, the underlying mechanisms responsible for inhibition of SK channel function among PVN neurons in AngII-Salt HTN remain unclear. It is well-known that intracellular calcium is one of the key regulators gating SK channel conductance. Here, we demonstrated the importance of intracellular calcium homeostasis in controlling neuronal excitability in PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) in vitro, and sympathetic nerve activity (SNA) and ABP in vivo. In whole-cell current-clamp recordings under brain...