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High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca 2+ Store

View Article: PubMed Central - PubMed

ABSTRACT

High salt (HS) intake sensitizes central autonomic circuitry leading to sympathoexcitation. However, its underlying mechanisms are not fully understood. We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca2+ store function would augment PVN neuronal excitability and sympathetic nerve activity (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce ER Ca2+ store function and increase excitability of PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) identified by retrograde label. PVN microinjection of the ER Ca2+ ATPase inhibitor thapsigargin (TG) increased SNA and mean arterial pressure (MAP) in a dose-dependent manner in rats with a normal salt (NS) diet (0.4%NaCl). In contrast, sympathoexcitatory responses to PVN TG were significantly (p < 0.05) blunted in HS treated rats compared to NS treatment. In whole cell current-clamp recordings from PVN-RVLM neurons, graded current injections evoked graded increases in spike frequency. Maximum discharge was significantly augmented (p < 0.05) by HS diet compared to NS group. Bath application of TG (0.5 μM) increased excitability of PVN-RVLM neurons in NS (p < 0.05), yet had no significant effect in HS rats. Our data indicate that HS intake augments excitability of PVN-RVLM neurons. Inhibition of the ER Ca2+-ATPase and depletion of Ca2+ store likely plays a role in increasing PVN neuronal excitability, which may underlie the mechanisms of sympathoexcitation in rats with chronic HS intake.

No MeSH data available.


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(A) PVN-RVLM neuron with red fluorescence from retrograde label (top) and same neuron with patch pipette positioned on cell surface with DIC microscopy (bottom). (B) Schematic drawings of coronal sections throughout the rat hypothalamus. Shaded area indicates spread of injected dye used to mark the injection sites in the bilateral PVN. The shape of each area was determined by overlaying tracings of the outermost diffusion area of injected dye (100 nl) through the rostral-caudal plane of the PVN. (C) Representative coronal slice through the PVN demonstrating spread of injected dye. AH, anterior hypothalamic area; 3V, third cerebral ventricle; RCh, retrochiasmatic area; MPO, medial preoptic nucleus; opt, optic tract; SOX, supraopticdecussation; StHy, striohypothalamic nucleus.
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Figure 6: (A) PVN-RVLM neuron with red fluorescence from retrograde label (top) and same neuron with patch pipette positioned on cell surface with DIC microscopy (bottom). (B) Schematic drawings of coronal sections throughout the rat hypothalamus. Shaded area indicates spread of injected dye used to mark the injection sites in the bilateral PVN. The shape of each area was determined by overlaying tracings of the outermost diffusion area of injected dye (100 nl) through the rostral-caudal plane of the PVN. (C) Representative coronal slice through the PVN demonstrating spread of injected dye. AH, anterior hypothalamic area; 3V, third cerebral ventricle; RCh, retrochiasmatic area; MPO, medial preoptic nucleus; opt, optic tract; SOX, supraopticdecussation; StHy, striohypothalamic nucleus.

Mentions: Injection sites were marked with 2% Chicago blue dye (100 nl). Coronal slices through the rostral caudal plane encompassing the PVN were examined to ensure microinjections were confined to the PVN as previously described by our laboratory (Larson et al., 2015a). Figure 6B shows the composite diffusion area of injected dye compiled by overlying brain slices from separate rats to demonstrate the outermost diffusion area. Distribution of injected dye was largely confined to the area encompassing the PVN (Figure 6C).


High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca 2+ Store
(A) PVN-RVLM neuron with red fluorescence from retrograde label (top) and same neuron with patch pipette positioned on cell surface with DIC microscopy (bottom). (B) Schematic drawings of coronal sections throughout the rat hypothalamus. Shaded area indicates spread of injected dye used to mark the injection sites in the bilateral PVN. The shape of each area was determined by overlaying tracings of the outermost diffusion area of injected dye (100 nl) through the rostral-caudal plane of the PVN. (C) Representative coronal slice through the PVN demonstrating spread of injected dye. AH, anterior hypothalamic area; 3V, third cerebral ventricle; RCh, retrochiasmatic area; MPO, medial preoptic nucleus; opt, optic tract; SOX, supraopticdecussation; StHy, striohypothalamic nucleus.
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Related In: Results  -  Collection

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Figure 6: (A) PVN-RVLM neuron with red fluorescence from retrograde label (top) and same neuron with patch pipette positioned on cell surface with DIC microscopy (bottom). (B) Schematic drawings of coronal sections throughout the rat hypothalamus. Shaded area indicates spread of injected dye used to mark the injection sites in the bilateral PVN. The shape of each area was determined by overlaying tracings of the outermost diffusion area of injected dye (100 nl) through the rostral-caudal plane of the PVN. (C) Representative coronal slice through the PVN demonstrating spread of injected dye. AH, anterior hypothalamic area; 3V, third cerebral ventricle; RCh, retrochiasmatic area; MPO, medial preoptic nucleus; opt, optic tract; SOX, supraopticdecussation; StHy, striohypothalamic nucleus.
Mentions: Injection sites were marked with 2% Chicago blue dye (100 nl). Coronal slices through the rostral caudal plane encompassing the PVN were examined to ensure microinjections were confined to the PVN as previously described by our laboratory (Larson et al., 2015a). Figure 6B shows the composite diffusion area of injected dye compiled by overlying brain slices from separate rats to demonstrate the outermost diffusion area. Distribution of injected dye was largely confined to the area encompassing the PVN (Figure 6C).

View Article: PubMed Central - PubMed

ABSTRACT

High salt (HS) intake sensitizes central autonomic circuitry leading to sympathoexcitation. However, its underlying mechanisms are not fully understood. We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca2+ store function would augment PVN neuronal excitability and sympathetic nerve activity (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce ER Ca2+ store function and increase excitability of PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) identified by retrograde label. PVN microinjection of the ER Ca2+ ATPase inhibitor thapsigargin (TG) increased SNA and mean arterial pressure (MAP) in a dose-dependent manner in rats with a normal salt (NS) diet (0.4%NaCl). In contrast, sympathoexcitatory responses to PVN TG were significantly (p < 0.05) blunted in HS treated rats compared to NS treatment. In whole cell current-clamp recordings from PVN-RVLM neurons, graded current injections evoked graded increases in spike frequency. Maximum discharge was significantly augmented (p < 0.05) by HS diet compared to NS group. Bath application of TG (0.5 μM) increased excitability of PVN-RVLM neurons in NS (p < 0.05), yet had no significant effect in HS rats. Our data indicate that HS intake augments excitability of PVN-RVLM neurons. Inhibition of the ER Ca2+-ATPase and depletion of Ca2+ store likely plays a role in increasing PVN neuronal excitability, which may underlie the mechanisms of sympathoexcitation in rats with chronic HS intake.

No MeSH data available.


Related in: MedlinePlus