ATP-sensitive K⁺channels in renal mitochondria

Abstract

Isolated kidney mitochondria swell when incubated in hyposmotic solutions containing K+ salts in a manner inhibited by ATP, ADP, 5-hydroxydecanoate, and glibenclamide and stimulated by GTP and diazoxide. These results suggest the existence of ATP-sensitive K+ channels in these mitochondria, similar to those previously described in heart, liver, and brain. Renal mitochondrial ATP-sensitive K+ uptake rates are ∼140 nmol·min–1·mg protein–1. This K+ transport results in a slight increase in respiration and decrease in the inner membrane potential. In addition, the activation of ATP-inhibited K+ uptake using diazoxide leads to a decrease of ATP hydrolysis through the reverse activity of the F0F1 ATP synthase when respiration is inhibited. In conclusion, we characterize an ATP-sensitive K+ transport pathway in kidney mitochondria that affects volume, respiration, and membrane potential and may have a role in the prevention of mitochondrial ATP hydrolysis.

F 1 F O-ATPase Activity and ATP Dependence of Mitochondrial Energization in Proximal Tubules after Hypoxia/Reoxygenation

“…However, the nonlinearity of formation of JC-1 red aggregates relative to ⌬⌿ m and their slow and incomplete dissociation back to monomers during de-energization limits the use of JC-1 to dynamically follow and manipulate the changes of ⌬⌿ m to gain more mechanistic information about the factors contributing to them (5). Safranin O is concentrated in the mitochondrial matrix as a linear function of ⌬⌿ m where its fluorescence is quenched, allowing its uptake and ⌬⌿ m to be followed by fluorescence changes (6)(7)(8). We have recently reported studies employing safranin O in digitonin-permeabilized tubule preparations to alternatively assess ⌬⌿ m in the model (5).…”

Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus

“…Microglial activation involves a metabolic reprograming that leads to potentiation of anaerobic glycolysis (Gimeno-Bayón et al, 2014), higher numbers of mitochondria labeled with [ 3 H]PK11195 (Bernal et al, 2009) and increased mitoK ATP channel expression . Activation of mitoK ATP channels increases potassium flux into the mitochondrial matrix and avoids excessive mitochondrial contraction that is deleterious for electron transport (Cancherini et al, 2003). Indeed, cells treated with Dzx demonstrate favorable energy profiles with limited damage following stress challenges (Iwai et al, 2000).…”

“…They act as metabolic sensors that regulate potassium flux and couple membrane excitability to cellular energy metabolism. K ATP channels are also located on the mitochondrial inner membrane, where they participate in the control of mitochondrial volume and ATP synthesis (Cancherini et al, 2003). It is clear that K ATP channel is a major component of the inflammatory response following brain injury.…”

The effect of ATP-dependent K(+)-channel opener on transmembrane potassium

“…АТР-зависимый вход K + через K + ATP -канал составляет значитель-ную долю транспорта K + в митохондриях, и его физиологическая значимость в настоящее время не вызывает сомнений. Исследования послед-него времени, в том числе и наши собственные, показали, что АТР-зависимый транспорт K + яв-ляется физиологически важным модулятором митохондриальных функций и энергозависи-мых процессов в митохондриях: дыхания [6][7][8], митохондриального объема [5], циклического транспорта K + [8], транспорта Са 2+ [9], синтеза АТР [7,10,11] и продукции активных форм кис-лорода (АФК) [12,13].…”

“…-канала близки к усло-виям полярографического метода, который ча-сто используют [6,7]. Данный подход позволяет выявить вклад K…”