Abstract 506: Long-term High Salt Intake Involves Reduced Small Conductance Ca2+-activated K+ (SK) Current in Pre-sympathetic Paraventricular Nucleus Neurons and Increased Sympathetic Nerve Activity (SNA)
It is well-documented that elevated sympathetic outflow is an important contributor to salt-sensitive hypertension. Accumulating evidence indicates that high salt (HS) intake is involved in the activation of the sympathetic nervous system. However, the neural mechanisms responsible for HS-induced sympathetic activation are not fully understood. Recently, we reported that hypertension resulting from angiotensin II and HS intake is characterized by reduced small conductance Ca2+-activated K+ (SK) current and increased excitability of RVLM projecting paraventricular nucleus (PVN-RVLM) neurons. Here, we hypothesized that HS intake may involve both reduced SK current in pre-sympathetic PVN neurons and increased neuronal excitability to contribute to the sympathetic activation. First, we determined whether 5 weeks of HS (2% NaCl) intake alters the SK current in PVN-RVLM neurons and whether this change affects the intrinsic excitability. In whole cell voltage-clamp recordings, the amplitude of SK current in neurons from the HS group (13 ± 5 pA, n=6) was significantly (P < 0.05) less than that from normal salt (NS, 0.4% NaCl) controls (63 ± 11 pA, n=6). In whole cell current-clamp recordings, graded current injections evoked graded increases in discharge frequency among neurons from both groups. Maximum discharge evoked by +200 pA current injection in the HS group was 43 ± 4 Hz (n=8), which was significantly greater (P < 0.01) than that of NS controls (22 ± 1 Hz, n=9). The SK channel blocker apamin (100 nM) significantly increased (P < 0.05) discharge in NS controls (47 ± 4 Hz, n=6), but had no effect in HS rats (45 ± 2 Hz, n=5). Next, the contribution of SK channel activity in regulating SNA was assessed by bilateral PVN microinjection of apamin in anesthetized rats with and without HS intake. Respectively, maximum increases in splanchnic SNA and renal SNA by apamin (12.5 pmol) were 319 ± 41% and 277 ± 48% in rats on a NS diet (n=6), contrasted by a much smaller increase of 116 ± 41% (P < 0.01) and 81 ± 28% (P < 0.01) in rats on HS (n=6). Our data indicate that reduced SK current in PVN-RVLM neurons contributes to the increased excitability in neurons from rats on a HS diet, which may be a contributing factor in the sympathetic activation that appears to accompany elevated salt intake.
- © 2012 by American Heart Association, Inc.