Opening of ATP sensitive potassium channels causes migraine attacks with aura

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.

Download Full-text

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

Clinical Science ◽

10.1042/cs0850319 ◽

1993 ◽

Vol 85 (3) ◽

pp. 319-325 ◽

Cited By ~ 7

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.

Download Full-text

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

Molecules ◽

10.3390/molecules26113233 ◽

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.

Download Full-text