scholarly journals Functional coupling between NMDA receptors and SK channels in rat hypothalamic magnocellular neurons: altered mechanisms during heart failure

2019 ◽  
Author(s):  
Hildebrando C. Ferreira‐Neto ◽  
Javier E. Stern
Keyword(s):  
Heart Failure ◽  
Nmda Receptors ◽  
Functional Coupling ◽  
Sk Channels ◽  
Magnocellular Neurons

scholarly journals Functional coupling between NMDA receptors and SK channels in rat hypothalamic magnocellular neurons: altered mechanisms during heart failure

2019 ◽  
Author(s):  
HC Ferreira-Neto ◽  
JE Stern
Keyword(s):  
Heart Failure ◽  
Nmda Receptors ◽  
Neuronal Activity ◽  
Functional Coupling ◽  
Pathophysiological Mechanism ◽  
Sk Channels ◽  
Excitatory Effect ◽  
Neurosecretory Neurons ◽  
Nmdar Activation ◽  
Patch Clamp Electrophysiology

ABSTRACTGlutamatergic NMDA receptors (NMDAR) and small conductance Ca2+-activated K+ channels (SK) are critical synaptic and intrinsic mechanisms that regulate the activity of hypothalamic magnocellular neurosecretory neurons (MNNs) under physiological and pathological states, including lactation and heart failure (HF). Still, whether NMDARs and SK channels in MNNs are functionally coupled, and whether changes in this coupling contribute to exacerbated neuronal activity during HF is at present unknown. In the present study, we addressed these questions using patch-clamp electrophysiology and confocal Ca2+ imaging in a rat model of ischaemic HF. We found that in MNNs of sham rats, blockade of SK channels with apamin (200 nM) significantly increased the magnitude of an NMDAR-evoked current (INMDA). We also observed that blockade of SK channels potentiated NMDAR-evoked firing, and abolished spike frequency adaptation in MNNs from sham, but not HF rats. Importantly, a larger INMDA-ΔCa2+response was observed under basal conditions in HF compared to sham rats. Finally, we found that dialyzing recorded cells with the Ca2+ chelator BAPTA (10 mM) increased the magnitude of INMDA in MNNs from both sham and HF rats, and occluded the effects of apamin in the former. Together, our studies demonstrate that in MNNs, NMDARs and SK channels are functionally coupled, forming a local negative feedback loop that restrains the excitatory effect evoked by NMDAR activation. Moreover, our studies also support a blunted NMDAR-SK channel coupling in MNNs of HF rats, standing thus as a pathophysiological mechanism contributing to exacerbated hypothalamic neuronal activity during this prevalent neurogenic cardiovascular disease.

scholarly journals A reduction in SK channels contributes to increased activity of hypothalamic magnocellular neurons during heart failure

2017 ◽  
Vol 595 (20) ◽  
pp. 6429-6442 ◽  
Author(s):  
Hildebrando C. Ferreira-Neto ◽  
Vinicia C. Biancardi ◽  
Javier E. Stern
Keyword(s):  
Heart Failure ◽  
Sk Channels ◽  
Magnocellular Neurons ◽  
Increased Activity

scholarly journals Functional Coupling of TRPV4, IK, and SK Channels Contributes to Ca2+-Dependent Endothelial Injury in Rodent Lung

2015 ◽  
Vol 5 (2) ◽  
pp. 279-290 ◽  
Author(s):  
Mike T. Lin ◽  
Ming-Yuan Jian ◽  
Mark S. Taylor ◽  
Donna L. Cioffi ◽  
Fui C. Yap ◽  
...  
Keyword(s):  
Endothelial Injury ◽  
Functional Coupling ◽  
Sk Channels

scholarly journals Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats

2013 ◽  
Vol 305 (4) ◽  
pp. R414-R422 ◽  
Author(s):  
Javier E. Stern ◽  
Evgeniy S. Potapenko
Keyword(s):  
Heart Failure ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Neuronal Activity ◽  
Receptor Activation ◽  
Membrane Depolarization ◽  
Neurosecretory Cells ◽  
Firing Activity ◽  
Nmda Current ◽  
Intracellular Ca

An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca2+ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca2+ levels (NMDA-ΔCa2+) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa2+ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa2+ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca2+ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca2+ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa2+ signaling during HF are discussed.

scholarly journals Functional Coupling of BK Channels to NMDA Receptors in Hippocampal Dentate Gyrus

2017 ◽  
Vol 112 (3) ◽  
pp. 112a ◽  
Author(s):  
Xin Guan ◽  
Jiyuan Zhang ◽  
Qin Li ◽  
Hui-Lin Pan ◽  
Jiusheng Yan
Keyword(s):  
Dentate Gyrus ◽  
Nmda Receptors ◽  
Bk Channels ◽  
Functional Coupling ◽  
Hippocampal Dentate Gyrus

scholarly journals HIF‐1α Increases Glutamatergic NMDA receptors in the PVN during chronic heart failure

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Neeru Sharma ◽  
Craig Cunningham ◽  
Xuefei Liu ◽  
Hong Zheng ◽  
Kaushik Patel
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Nmda Receptors

scholarly journals Structural and Functional Coupling between BK Channels and NMDA Receptors

2016 ◽  
Vol 110 (3) ◽  
pp. 289a
Author(s):  
Jiyuan Zhang ◽  
Qin Li ◽  
Xin Guan ◽  
Hui-Lin Pan ◽  
Jiusheng Yan
Keyword(s):  
Nmda Receptors ◽  
Bk Channels ◽  
Functional Coupling
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