KATP channel opening does not contribute significantly to the vasodilatory effect of SH-group-containing ACE inhibitors

1996 ◽  
Vol 11 (4) ◽  
pp. 192-196 ◽  
Author(s):  
H. Köppel ◽  
S. Holzmann ◽  
W. Klein ◽  
E. Horn ◽  
S. Horn ◽  
...  
Keyword(s):  
Ace Inhibitors ◽  
Katp Channel ◽  
Vasodilatory Effect ◽  
Channel Opening ◽  
Sh Group

Effects of thiol-modifying agents on KATP channels in guinea pig ventricular cells

1995 ◽  
Vol 269 (5) ◽  
pp. H1625-H1633 ◽  
Author(s):  
W. A. Coetzee ◽  
T. Y. Nakamura ◽  
J. F. Faivre
Keyword(s):  
Katp Channel ◽  
Single Channel ◽  
Katp Channels ◽  
Channel Activity ◽  
Nitrobenzoic Acid ◽  
Ventricular Cells ◽  
Channel Opening ◽  
Sh Group ◽  
Constant Potential ◽  
High Degree

ATP-sensitive K+ (KATP) channels are thought only to open during conditions of metabolic impairment (e.g., myocardial ischemia). However, the regulation of KATP channel opening during ischemia remains poorly understood. We tested whether thiol (SH) group oxidation, which is known to occur during ischemia, may be involved in KATP channel regulation. Inside-out membrane patches were voltage clamped at a constant potential (O mV) in asymmetrical K+ solutions. The effects of compounds that specifically modify SH groups [p-chloromercuri-phenylsulfonic acid (pCMPS), 5-5'-dithio-bis(2-nitrobenzoic acid) [DTNB], and thimerosal] were tested. The membrane-impermeable compound, pCMPS (> or = 5 microM), caused a quick and irreversible inhibition of KATP channel activity. The reducing agent, dl-dithiothreitol (DTT) (3 mM) was able to reverse this inhibition. DTNB (500 microM) caused a rapid, but spontaneously reversible, block of KATP channel activity. After DTNB, no change was observed in single channel conductance. Oxidized glutathione (GSSG, 3 mM) did not block KATP channel activity. Thimerosal (100-500 microM) induced a DTT-reversible block of partially rundown KATP channels, or channels that underwent complete rundown; these channels were reactivated with trypsin (1 mg/ml). Thimerosal did not block KATP channels that had a high degree of activity. However, the ATP sensitivity was decreased; the concentration of ATP needed to half-maximally inhibit the channel (Ki) was increased from 47 +/- 12 to 221 +/- 35 microM (n = 6, P < 0.05). This was not due to a spontaneous change with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective mitochondrial KATP channel opening controls human myocardial preconditioning: Too much of a good thing?

Surgery ◽  
2000 ◽  
Vol 128 (2) ◽  
pp. 368-373 ◽  
Author(s):  
Benjamin J. Pomerantz ◽  
Thomas N. Robinson ◽  
Julie K. Heimbach ◽  
Casey M. Calkins ◽  
Stephanie A. Miller ◽  
...  
Keyword(s):  
Katp Channel ◽  
Good Thing ◽  
Mitochondrial Katp Channel ◽  
Myocardial Preconditioning ◽  
Channel Opening

Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by KATP—Channel opening

Resuscitation ◽  
2014 ◽  
Vol 85 (6) ◽  
pp. 826-832 ◽  
Author(s):  
Anne Brücken ◽  
Pinar Kurnaz ◽  
Christian Bleilevens ◽  
Matthias Derwall ◽  
Joachim Weis ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Katp Channel ◽  
Noble Gas ◽  
Channel Opening ◽  
Dose Dependent

scholarly journals The analgesic effect of dipyrone in peripheral tissue involves two different mechanisms: Neuronal KATP channel opening and CB1 receptor activation

2014 ◽  
Vol 741 ◽  
pp. 124-131 ◽  
Author(s):  
Gilson Gonçalves dos Santos ◽  
Elayne Vieira Dias ◽  
Juliana Maia Teixeira ◽  
Maria Carolina Pedro Athie ◽  
Ivan José Magayewski Bonet ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Katp Channel ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Peripheral Tissue ◽  
Channel Opening

scholarly journals Regulation of Cloned Atp-Sensitive K Channels by Adenine Nucleotides and Sulfonylureas

2001 ◽  
Vol 118 (4) ◽  
pp. 391-406 ◽  
Author(s):  
Scott A. John ◽  
James N. Weiss ◽  
Bernard Ribalet
Keyword(s):  
Katp Channel ◽  
Adenine Nucleotides ◽  
Katp Channels ◽  
Functional Coupling ◽  
Sulfonylurea Receptor ◽  
K Channels ◽  
Channel Regulation ◽  
Channel Opening ◽  
Insight Into ◽  
Positively Charged

KATP channels, comprised of the pore-forming protein Kir6.x and the sulfonylurea receptor SURx, are regulated in an interdependent manner by adenine nucleotides, PIP2, and sulfonylureas. To gain insight into these interactions, we investigated the effects of mutating positively charged residues in Kir6.2, previously implicated in the response to PIP2, on channel regulation by adenine nucleotides and the sulfonylurea glyburide. Our data show that the Kir6.2 “PIP2-insensitive” mutants R176C and R177C are not reactivated by MgADP after ATP-induced inhibition and are also insensitive to glyburide. These results suggest that R176 and R177 are required for functional coupling to SUR1, which confers MgADP and sulfonylurea sensitivity to the KATP channel. In contrast, the R301C and R314C mutants, which are also “PIP2-insensitive,” remained sensitive to stimulation by MgADP in the absence of ATP and were inhibited by glyburide. Based on these findings, as well as previous data, we propose a model of the KATP channel whereby in the presence of ATP, the R176 and R177 residues on Kir6.2 form a specific site that interacts with NBF1 bound to ATP on SUR1, promoting channel opening by counteracting the inhibition by ATP. This interaction is facilitated by binding of MgADP to NBF2 and blocked by binding of sulfonylureas to SUR1. In the absence of ATP, since KATP channels are not blocked by ATP, they do not require the counteracting effect of NBF1 interacting with R176 and R177 to open. Nevertheless, channels in this state remain activated by MgADP. This effect may be explained by a direct stimulatory interaction of NBF2/MgADP moiety with another region of Kir6.2 (perhaps the NH2 terminus), or by NBF2/MgADP still promoting a weak interaction between NBF1 and Kir6.2 in the absence of ATP. The region delimited by R301 and R314 is not involved in the interaction with NBF1 or NBF2, but confers additional PIP2 sensitivity.

Isoflurane Facilitates Cardiac Sarcolemmal KATP Channel Opening Via G-Proteins

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A668
Author(s):  
Susanne Gassmayr ◽  
Anna Stadnicka ◽  
Wai-Meng Kwok ◽  
Zeljko Bosnjak
Keyword(s):  
G Proteins ◽  
Katp Channel ◽  
Channel Opening

scholarly journals The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

2017 ◽  
Vol 41 (3) ◽  
pp. 1020-1034 ◽  
Author(s):  
Weijie Liang ◽  
Meiji Chen ◽  
Dongdan Zheng ◽  
Jianhao Li ◽  
Mingcai Song ◽  
...  
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Katp Channel ◽  
Channel Blocker ◽  
Cardiac Injury ◽  
Cardiac Cells ◽  
Mitochondrial Katp Channel ◽  
Channel Opening ◽  
Pre Treatment

Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS), toll-like receptor 4 (TLR4), receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis), which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP) channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG) to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP) and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis) or TAK-242 (an inhibitor of TLR4) co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener) or pinacidil (Pin, a non-selective KATP channel opener) or N-acetyl-L-cysteine (NAC, a ROS scavenger) pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker) or glibenclamide (Gli, a non-selective KATP channel blocker) pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

ATP triggers Katp channel opening without hydrolysis

2019 ◽  
Author(s):  
J Sikimic ◽  
J Bryan ◽  
P Krippeit-Drews ◽  
G Drews
Keyword(s):  
Katp Channel ◽  
Channel Opening
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