Altered expression of delayed excitation in medial NTS neurons of spontaneously hypertensive rats

Sundaram, Kalyana; Johnson, Stephen M.; Felder, Robert B.

doi:10.1016/s0304-3940(97)00214-0

Cited by 13 publications

(14 citation statements)

References 16 publications

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“…A previous study reported a reduced duration of delayed excitation in NTS neurons from spontaneously hypertensive rats (Sundaram et al 1997); therefore the changes reported here may be a general consequence of hypertension regardless of the underlying etiology of the hypertension. The A-type K channel (I A ) has also been reported to be altered in sympathetic, superior cervical ganglia in spontaneously hypertensive rat (Robertson and Schofield 1999); however, the mechanisms appear more complicated than reported for NTS neurons in this report.…”

Section: Ap Parameters In Nts Neurons With Delayed Excitationsupporting

confidence: 65%

“…NTS neurons with prominent delayed excitation are most likely second-order neurons in the arterial baroreflex receiving C-fiber afferent inputs (Bailey et al 2002). While it is likely that the delay to the first AP is only partly mediated by TOCs (Hattori 2003;Liss 2001;Sundaram et al 1997), our analysis revealed no differences in NT and HT neurons in delayed and steady-state TEA-sensitive K-currents in Ca 2ϩ -containing or Ca 2ϩ -free solutions. While the contribution of TOCs to the responses of NTS neurons to depolarization has been repeatedly shown, the significance of TOCs in the regulation of neuro-humoral status has been difficult to discern.…”

Section: Ap Parameters In Nts Neurons With Delayed Excitationmentioning

confidence: 50%

“…Delayed excitation is defined as a delay in the occurrence of an action potential (AP) response to depolarization after hyperpolarization and is primarily attributed to TOCs. Delayed excitation has been reported to be reduced in NTS neurons in the spontaneously hypertensive rat (Sundaram et al 1997).…”

Section: Introductionmentioning

confidence: 96%

“…NTS neurons receiving afferent inputs from the arterial baroreceptors express considerable voltage-dependent activation of transient outward potassium conductances (TOCs), and as a result, delayed excitation is an essential feature of most of these neurons (Bailey et al 2002;Paton et al 1993;Sundaram et al 1997). Functionally, microinjection into the NTS of 4-aminopyridine (4-AP), an antagonist of TOCs and delayed excitation, attenuates baroreflex regulation of heart rate (Butcher and Paton 1998).…”

Section: Introductionmentioning

confidence: 99%

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Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Belugin

Mifflin²

2005

Journal of Neurophysiology

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Belugin, Sergei and Steve Mifflin. Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats. J Neurophysiol 94: 3849 -3859, 2005; doi:10.1152/jn.00573.2005. Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltagedependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 Ϯ 5 mmHg, n ϭ 26, P Ͻ 0.001) rats compared with normotensive (NT) rats (109 Ϯ 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from Ϫ10 to ϩ10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P Ͻ 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine-sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P Ͻ 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60 -80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n ϭ 8 cells, P ϭ 0.022) than DiA-labeled neurons from NT rats (n ϭ 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P ϭ 0.016 and P ϭ 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P ϭ 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.

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Section: Ap Parameters In Nts Neurons With Delayed Excitationsupporting

confidence: 65%

Section: Ap Parameters In Nts Neurons With Delayed Excitationmentioning

confidence: 50%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Belugin

Mifflin²

2005

Journal of Neurophysiology

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“…Neurons showing a delayed return to baseline following the pulse due to a prominent A-type K ϩ current are termed delayed excitation (DE) cells, those with a postinhibitory rebound (PIR) action potential due to a prominent low threshold Ca 2ϩ current are called PIR cells, and those with neither of these responses are NON cells (27). Since DE neurons have specifically been identified as exerting important control over autonomic processes (11,24), we investigated whether nesfatin-1 would have selective effects on this specific cell type. Nesfatin-1 influenced the membrane potential of DE (70% depolarize, 15% hyperpolarize, 15% no responsen ϭ 13, Fig.…”

Section: Nesfatin-1 Influences the Excitability Of Mnts Neuronsmentioning

confidence: 99%

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Mimee

Smith

Ferguson

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Nesfatin-1 has been identified as one of the most potent centrally acting anorexigenic peptides, and it has also been shown to play important roles in the control of cardiovascular function. In situ hybridization and immunohistochemical studies have revealed the expression of nesfatin-1 throughout the brain and, in particular, in the medullary autonomic gateway known as the nucleus of the solitary tract (NTS). The present study was thus undertaken to explore the cellular correlates and functional roles of nesfatin-1 actions in the medial NTS (mNTS). Using current-clamp electrophysiology recordings from mNTS neurons in slice preparation, we show that bathapplied nesfatin-1 directly influences the excitability of the majority of mNTS neurons by eliciting either depolarizing (42%, mean: 7.8 Ϯ 0.8 mV) or hyperpolarizing (21%, mean: Ϫ8. 2 Ϯ 1.0 mV) responses. These responses were observed in all electrophysiologically defined cell types in the NTS and were site specific and concentration dependent. Furthermore, post hoc single cell reverse transcriptase polymerase reaction revealed a depolarizing action of nesfatin-1 on NPY and nucleobindin-2-expressing mNTS neurons. We have also correlated these actions of nesfatin-1 on neuronal membrane potential with physiological outcomes, using in vivo microinjection techniques to demonstrate that nesfatin-1 microinjected into the mNTS induces significant increases in both blood pressure (mean AUC ϭ 3354.1 Ϯ 750.7 mmHg·s, n ϭ 6) and heart rate (mean AUC ϭ 164.8 Ϯ 78.5 beats, n ϭ 6) in rats. Our results provide critical insight into the circuitry and physiology involved in the profound effects of nesfatin-1 and highlight the NTS as a key structure mediating these autonomic actions. microinjection; platch clamp; peptides NESFATIN-1 has been identified as one of the most potent centrally acting anorexigenic peptides (17). An 82 amino acid cleavage product of the nucleobindin-2 (NUCB2) protein, nesfatin-1 acutely and chronically reduces feeding in rodents when injected either intracerebroventricularly or peripherally, and these effects are dependent on melanocortin and oxytocin signaling (16,17,22,29). Furthermore, treatment with nesfatin-1 neutralizing antibodies markedly increases food consumption and weight gain in animals, underscoring the critical physiological, tonic inhibitory control this peptide exerts over ingestive behaviors (17). In addition to its remarkable effects on food intake, nesfatin-1 has also been shown to play important roles in the control of cardiovascular function, water intake, blood glucose regulation, stress responses, and puberty onset (6,8,23,28).In line with its numerous functions, comprehensive immunohistochemical studies have revealed a widespread distribution of nesfatin-1 throughout the brain. Notably, the nesfatin-1 peptide is strongly expressed in regions involved in the control of energy homeostasis and autonomic function in both hypothalamic and medullary centres (5), including the autonomic gateway known as the nucleus of the solitary tract (...

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Angiotensin II Inhibits the A-type K⁺ Current of Hypothalamic Paraventricular Nucleus Neurons in Rats with Heart Failure: Role of MAPK-ERK1/2 Signaling

Roy

Ferreira‐Neto

Felder

et al. 2021

Preprint

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ANGII-mediated sympathohumoral activation constitutes a key pathophysiological mechanism in heart failure (HF). While the hypothalamic paraventricular nucleus (PVN) is recognized as a major site mediating ANGII effects in HF, the precise mechanisms by which ANGII influences sympathohumoral outflow from the PVN remain unknown. ANGII activates the ubiquitous intracellular MAPK signaling cascades and recent studies revealed a key role for ERK1/2 MAPK signaling in ANGII-mediated sympathoexcitation in HF rats. Importantly, ERK1/2 was reported to inhibit the transient outward potassium current (IA) in hippocampal neurons. Given that IA is a critical determinant of the PVN neuronal excitability, and that downregulation of IA in the brain has been reported in cardiovascular disease states, including HF, we investigated here whether ANGII modulates IA in PVN neurons via the MAPK-ERK pathway, and, whether these effects are altered in HF rats. Patch-clamp recordings from identified magnocellular neurosecretory (MNNs) and presympathetic (PS) PVN neurons revealed that ANGII inhibited IA in both PVN neuronal types, both in sham and HF rats. Importantly, ANGII effects were blocked by inhibiting MAPK-ERK signaling as well as by inhibiting EGFR, a gateway to MAPK-ERK signaling. While no differences in basal IA magnitude were found between sham and HF rats under normal conditions, MAPK-ERK blockade resulted in significantly larger IA in both PVN neuronal types in HF rats. Taken together, our studies show that ANGII-induced ERK1/2 activity inhibits IA and increases the excitability of presympathetic and neuroendocrine PVN neurons, contributing to the neurohumoral overactivity than promotes progression of the HF syndrome.

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Altered expression of delayed excitation in medial NTS neurons of spontaneously hypertensive rats

Cited by 13 publications

References 16 publications

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Angiotensin II Inhibits the A-type K⁺ Current of Hypothalamic Paraventricular Nucleus Neurons in Rats with Heart Failure: Role of MAPK-ERK1/2 Signaling

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Altered expression of delayed excitation in medial NTS neurons of spontaneously hypertensive rats

Cited by 13 publications

References 16 publications

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Transient Voltage-Dependent Potassium Currents Are Reduced in NTS Neurons Isolated From Renal Wrap Hypertensive Rats

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Angiotensin II Inhibits the A-type K+ Current of Hypothalamic Paraventricular Nucleus Neurons in Rats with Heart Failure: Role of MAPK-ERK1/2 Signaling

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Angiotensin II Inhibits the A-type K⁺ Current of Hypothalamic Paraventricular Nucleus Neurons in Rats with Heart Failure: Role of MAPK-ERK1/2 Signaling