scholarly journals An increased extrasynaptic NMDA tone inhibits A-type K+current and increases excitability of hypothalamic neurosecretory neurons in hypertensive rats

2017 ◽  
Vol 595 (14) ◽  
pp. 4647-4661 ◽  
Author(s):  
Meng Zhang ◽  
Vinicia C. Biancardi ◽  
Javier E. Stern
Keyword(s):  
Hypertensive Rats ◽  
Type K ◽  
Neurosecretory Neurons ◽  
K Current

scholarly journals Exacerbated effects of prorenin on hypothalamic magnocellular neuronal activity and vasopressin plasma levels during salt-sensitive hypertension

2019 ◽  
Vol 317 (3) ◽  
pp. H496-H504
Author(s):  
Soledad Pitra ◽  
Caleb J. Worker ◽  
Yumei Feng ◽  
Javier E. Stern
Keyword(s):  
Plasma Levels ◽  
Renin Angiotensin System ◽  
Membrane Excitability ◽  
Hypertensive Rats ◽  
Deoxycorticosterone Acetate ◽  
Type K ◽  
Neurosecretory Neurons ◽  
Salt Hypertension ◽  
Underlying Mechanisms ◽  
Salt Sensitive Hypertension

Accumulating evidence supports that the brain renin-angiotensin system (RAS), including prorenin (PR) and its receptor (PRR), two newly discovered RAS players, contribute to sympathoexcitation in salt-sensitive hypertension. Still, whether PR also contributed to elevated circulating levels of neurohormones such as vasopressin (VP) during salt-sensitive hypertension, and if so, what are the precise underlying mechanisms, remains to be determined. To address these questions, we obtained patch-clamp recordings from hypothalamic magnocellular neurosecretory neurons (MNNs) that synthesize the neurohormones oxytocin and VP in acute hypothalamic slices obtained from sham and deoxycorticosterone acetate (DOCA)-salt-treated hypertensive rats. We found that focal application of PR markedly increased membrane excitability and firing responses in MNNs of DOCA-salt, compared with sham rats. This effect included a shorter latency to spike initiation and increased numbers of spikes in response to depolarizing stimuli and was mediated by a more robust inhibition of A-type K+ channels in DOCA-salt compared with sham rats. On the other hand, the afterhyperpolarizing potential mediated by the activation of Ca2+-dependent K+ channel was not affected by PR. mRNA expression of PRR, VP, and the Kv4.3 K+ channel subunit in the supraoptic nucleus of DOCA-salt hypertensive rats was increased compared with sham rats. Finally, we report a significant decrease of plasma VP levels in neuron-selective PRR knockdown mice treated with DOCA-salt, compared with wild-type DOCA-salt-treated mice. Together, these results support that activation of PRR contributes to increased excitability and firing discharge of MNNs and increased plasma levels of VP in DOCA-salt hypertension. NEW & NOTEWORTHY Our studies support that prorenin (PR) and its receptor (PRR) within the hypothalamus contribute to elevated plasma vasopressin levels in deoxycorticosterone acetate-salt hypertension, in part because of an exacerbated effect of PR on magnocellular neurosecretory neuron excitability; Moreover, our study implicates A-type K+ channels as key underlying molecular targets mediating these effects. Thus, PR/PRR stands as a novel therapeutic target for the treatment of neurohumoral activation in salt-sensitive hypertension.

Clofilium-induced Block of Delayed Rectifier Type K+Current in Atrial Tumor Cells (AT-1 Cells)

1997 ◽  
Vol 29 (1) ◽  
pp. 301-307 ◽  
Author(s):  
Mohit Lal Bhattacharyya ◽  
Shukla Sarker ◽  
Kawonia P Mull ◽  
Qadriyyah Debnam
Keyword(s):  
Tumor Cells ◽  
Delayed Rectifier ◽  
Type K ◽  
K Current ◽  
Atrial Tumor

Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats

1993 ◽  
Vol 264 (5) ◽  
pp. H1337-H1345 ◽  
Author(s):  
S. K. England ◽  
T. A. Wooldridge ◽  
W. J. Stekiel ◽  
N. J. Rusch
Keyword(s):  
Single Channel ◽  
Muscle Cells ◽  
Ca Channel ◽  
Ca Channels ◽  
Hypertensive Rats ◽  
Genetically Hypertensive Rats ◽  
K Current ◽  
Inside Out ◽  
Genetically Hypertensive ◽  
Arterial Muscle

Arterial smooth muscle from hypertensive rats shows an increased membrane permeability to K+ that depends on Ca2+ influx. To define the mechanism of this membrane alteration, we tested the hypothesis that Ca(2+)-dependent K+ current (IK(Ca)) is increased in arterial muscle membranes from genetically hypertensive rats. Single-channel K+ currents measured in cell-attached and inside-out aortic membrane patches from spontaneously hypertensive rats (SHR) were compared with those from normotensive Wistar-Kyoto rats (WKY). Inside-out patches from both rat strains showed a predominant 225 pS, Ca(2+)- and voltage-dependent K+ channel in symmetrical 145 mM KCl solutions, which was blocked by tetraethylammonium [concentration for half-maximal block (IC50) < or = 0.3 mM]. In cell-attached patches of aortic muscle cells bathed in physiological salt solution, this channel [IK(Ca) channel] showed a fivefold higher open-state probability (NPo) in SHR as compared with WKY. This increased NPo of SHR IK(Ca) channels in membranes of intact aortic muscle cells was not correlated with an altered membrane potential in current-clamped SHR myocytes or with changes in cytosolic free Ca2+ concentration in fura-2-loaded aortic muscle cells. However, inside-out aortic membrane patches from SHR showed more detected IK(Ca) channels per patch, a higher IK(Ca) channel NPo, and a greater total patch current than their WKY counterparts. Further analysis revealed a greater Ca2+ sensitivity of SHR than WKY IK(Ca) channels. These results suggest that IK(Ca) channel function is altered in isolated membrane patches of arterial muscle from genetically hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Involvement of the 4-aminopyridine-sensitive transient A-type K+current in macrophage-induced neuronal injury

2010 ◽  
Vol 31 (2) ◽  
pp. 214-222 ◽  
Author(s):  
Dehui Hu ◽  
Jianuo Liu ◽  
James Keblesh ◽  
Huangui Xiong
Keyword(s):  
Neuronal Injury ◽  
Type K ◽  
K Current

scholarly journals The selective A-type K+ current blocker Tx3-1 isolated from the Phoneutria nigriventer venom enhances memory of naïve and Aβ25-35-treated mice

Toxicon ◽  
2013 ◽  
Vol 76 ◽  
pp. 23-27 ◽  
Author(s):  
Guilherme M. Gomes ◽  
Gerusa D. Dalmolin ◽  
Marta do Nascimento Cordeiro ◽  
Marcus V. Gomez ◽  
Juliano Ferreira ◽  
...  
Keyword(s):  
Type K ◽  
K Current ◽  
Phoneutria Nigriventer
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