scholarly journals Identification of the Large-Conductance Ca2+-Regulated Potassium Channel in Mitochondria of Human Bronchial Epithelial Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3233
Author(s):  
Aleksandra Sek ◽  
Rafal P. Kampa ◽  
Bogusz Kulawiak ◽  
Adam Szewczyk ◽  
Piotr Bednarczyk
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Epithelial Cell Line ◽  
Bkca Channel ◽  
Channel Activity ◽  
Potassium Channel Opener ◽  
Patch Clamp Technique ◽  
Bkca Channels ◽  
Bronchial Epithelial ◽  
Channel Opener

Mitochondria play a key role in energy metabolism within the cell. Potassium channels such as ATP-sensitive, voltage-gated or large-conductance Ca2+-regulated channels have been described in the inner mitochondrial membrane. Several hypotheses have been proposed to describe the important roles of mitochondrial potassium channels in cell survival and death pathways. In the current study, we identified two populations of mitochondrial large-conductance Ca2+-regulated potassium (mitoBKCa) channels in human bronchial epithelial (HBE) cells. The biophysical properties of the channels were characterized using the patch-clamp technique. We observed the activity of the channel with a mean conductance close to 285 pS in symmetric 150/150 mM KCl solution. Channel activity was increased upon application of the potassium channel opener NS11021 in the micromolar concentration range. The channel activity was completely inhibited by 1 µM paxilline and 300 nM iberiotoxin, selective inhibitors of the BKCa channels. Based on calcium and iberiotoxin modulation, we suggest that the C-terminus of the protein is localized to the mitochondrial matrix. Additionally, using RT-PCR, we confirmed the presence of α pore-forming (Slo1) and auxiliary β3-β4 subunits of BKCa channel in HBE cells. Western blot analysis of cellular fractions confirmed the mitochondrial localization of α pore-forming and predominately β3 subunits. Additionally, the regulation of oxygen consumption and membrane potential of human bronchial epithelial mitochondria in the presence of the potassium channel opener NS11021 and inhibitor paxilline were also studied. In summary, for the first time, the electrophysiological and functional properties of the mitoBKCa channel in a bronchial epithelial cell line were described.

Isoflurane Sensitizes the Cardiac Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel to Pinacidil

2003 ◽  
Vol 98 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Susanne Gassmayr ◽  
Anna Stadnicka ◽  
Akihiro Suzuki ◽  
Wai-Meng Kwok ◽  
Zeljko J. Bosnjak
Keyword(s):  
Potassium Channel ◽  
Signaling Pathways ◽  
Adenosine Triphosphate ◽  
Intracellular Signaling ◽  
Kinase Inhibitor ◽  
Potassium Channel Opener ◽  
Patch Clamp Technique ◽  
Channel Opener ◽  
Current Activation ◽  
Sensitization Effect

Background Cardioprotective effects of isoflurane are partially mediated by the sarcolemmal adenosine triphosphate-sensitive potassium (sarcK ATP ) channel. The authors tested the hypothesis that isoflurane sensitizes sarcK ATP channels to a potassium channel opener, pinacidil, adenosine- and phospholipid-mediated pathways. Methods Activation by pinacidil of the K ATP current (I KATP ) was monitored in guinea pig ventricular myocytes at 0.5 and 5 mm intracellular ATP in the whole cell configuration of the patch clamp technique. The sensitization effect was evaluated by pretreating each myocyte with isoflurane (0.57 +/- 0.04 mm) before application of pinacidil (5 micro m) in the continued presence of the anesthetic. To investigate whether intracellular signaling pathways may be involved in isoflurane sensitization, the authors used the adenosine receptor antagonist theophylline (100 micro m) and the phosphatidylinositol kinase inhibitor wortmannin (100 micro m). Results The density of pinacidil-activated I KATP was higher at 0.5 mm ATP (20.7 +/- 3.2 pA/pF) than at 5 mm ATP (2.0 +/- 0.3 pA/pF). At 0.5 mm ATP, pretreatment with isoflurane caused an increase in density of pinacidil-activated I KATP (42.4 +/- 6.2 pA/pF) and accelerated the rate of current activation (from 5.4 +/- 1.2 to 39.0 +/- 7.9 pA. pF(-1). min(-1) ). Theophylline attenuated current activation by pinacidil (9.4 +/- 3.9 pA/pF) and abolished the sensitization effect of isoflurane on I KATP (10.0 +/- 2.5 pA/pF). Wortmannin did not alter pinacidil activation of I KATP (13.2 +/- 1.7 pA/pF) but prevented sensitization by isoflurane (15.8 +/- 4.5 pA/pF). Conclusions These results suggest that isoflurane increases sensitivity of cardiac sarcK ATP channels to the potassium channel opener pinacidil. Blockade of adenosine receptors or phosphatidylinositol kinases abolishes the sensitization effect, suggesting that the adenosine and phospholipid signaling pathways may be involved in the actions by isoflurane.

Potassium Channels in Hypokalaemic Periodic Paralysis: A Key to the Pathogenesis?

1993 ◽  
Vol 85 (3) ◽  
pp. 319-325 ◽  
Author(s):  
T. P. Links ◽  
A. J. Smit ◽  
H. J. G. H. Oosterhuis ◽  
W. D. Reitsma
Keyword(s):  
Muscle Strength ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Insulin Release ◽  
Periodic Paralysis ◽  
Potassium Channel Opener ◽  
Glucose Loading ◽  
Control Subjects ◽  
Channel Opener ◽  
Hypokalaemic Periodic Paralysis

1. A possible role for the ATP-sensitive potassium channels in the pathogenesis of hypokalaemic periodic paralysis was investigated. 2. We assessed insulin release and muscle strength after intravenous glucose loading with and without the potassium channel opener pinacidil and the potassium channel blocker glibenclamide in three patients with hypokalaemic periodic paralysis and in a pair of matched control subjects for each patient. 3. A significantly higher initial insulin response (1.5-30 min) was found in the patients with hypokalaemic periodic paralysis in comparison with the control subjects. During potassium channel blocking with glibenclamide the insulin release was more enhanced in patients than in control subjects. On the other hand, the potassium channel opener pinacidil impaired the insulin release in healthy control subjects but not in patients. The serum glucose levels showed no differences between patients and control subjects. In one of the patients with hypokalaemic periodic paralysis glucose loading resulted in a fall in muscle strength, which did not occur during the administration of pinacidil. 4. These findings suggest a disturbance in the ATP-sensitive potassium channel in patients with hypokalaemic periodic paralysis, which is not limited to pancreatic β cells, but may be also involved in the abnormal behaviour of skeletal muscle.

scholarly journals Opening of ATP sensitive potassium channels causes migraine attacks with aura

Brain ◽  
2021 ◽  
Author(s):  
Mohammad Al-Mahdi Al-Karagholi ◽  
Hashmat Ghanizada ◽  
Cherie Amalie Waldorff Nielsen ◽  
Anders Hougaard ◽  
Messoud Ashina
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Migraine With Aura ◽  
Migraine Headache ◽  
Migraine Aura ◽  
Potassium Channel Opener ◽  
Pathophysiological Mechanisms ◽  
Channel Opener ◽  
The Common ◽  
Years Lived With Disability

Abstract Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in migraine with aura patients.

scholarly journals Remodeling of Arterial Tone Regulation in Postnatal Development: Focus on Smooth Muscle Cell Potassium Channels

2021 ◽  
Vol 22 (11) ◽  
pp. 5413
Author(s):  
Anastasia A. Shvetsova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova ◽  
Rudolf Schubert
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Postnatal Development ◽  
Sympathetic Innervation ◽  
Treatment Strategies ◽  
Muscle Membrane ◽  
Postnatal Life ◽  
Vascular Control ◽  
Bkca Channels

Maturation of the cardiovascular system is associated with crucial structural and functional remodeling. Thickening of the arterial wall, maturation of the sympathetic innervation, and switching of the mechanisms of arterial contraction from calcium-independent to calcium-dependent occur during postnatal development. All these processes promote an almost doubling of blood pressure from the moment of birth to reaching adulthood. This review focuses on the developmental alterations of potassium channels functioning as key smooth muscle membrane potential determinants and, consequently, vascular tone regulators. We present evidence that the pattern of potassium channel contribution to vascular control changes from Kir2, Kv1, Kv7 and TASK-1 channels to BKCa channels with maturation. The differences in the contribution of potassium channels to vasomotor tone at different stages of postnatal life should be considered in treatment strategies of cardiovascular diseases associated with potassium channel malfunction.

scholarly journals Effect of an ATP-Regulated Potassium Channel Opener, Nicorandil, on Isolated Outer Hair Cells of the Guinea Pig Cochlea

1998 ◽  
Vol 1998 (Supplement96) ◽  
pp. 23-30
Author(s):  
Akimitsu Kawai ◽  
Yukihiro Sato ◽  
Takeshi Akisada ◽  
Tsuyoshi Yoshihiro ◽  
Kotaro Take ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Potassium Channel ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Potassium Channel Opener ◽  
Guinea Pig Cochlea ◽  
Channel Opener
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