Subconductance states of mitochondrial chloride channels: implication for functionally-coupled tetramers.

Recently, it has been discovered that isoforms of intracellular chloride channels (CLIC) are present in cardiac mitochondria. By reconstituting rat cardiac mitochondrial chloride channels into bilayer lipid membranes, we detected three equally separated subconductance states with conductance increment of 45 pS and < 2% occupancy. The observed rare events of channel decomposition into substates, accompanied by disrupted gating, provide an insight into channel quaternary structure.

Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels.

H2S donor molecules have the potential to be viable therapeutic agents. The aim of this current study was (i) to investigate the effects of a novel triphenylphosphonium derivatised dithiolethione (AP39), in the presence and absence of reduced nitric oxide bioavailability and (ii) to determine the effects of AP39 on myocardial membrane channels; CaV3, RyR2 and Cl(-). Normotensive, L-NAME- or phenylephrine-treated rats were administered Na2S, AP39 or control compounds (AP219 and ADT-OH) (0.

Mitochondrial chloride channels: electrophysiological characterization and pH induction of channel pore dilation.

Physiological and pathological functions of mitochondria are highly dependent on the properties and regulation of mitochondrial ion channels. There is still no clear understanding of the molecular identity, regulation, and properties of anion mitochondrial channels. The inner membrane anion channel (IMAC) was assumed to be equivalent to mitochondrial centum picosiemens (mCS).

Low molecular thiols, pH and O2 modulate H2S-induced S-nitrosoglutathione decomposition - •NO release.

We studied the involvement of O2, pH and low molecular thiols in H2S-induced decomposition of S-nitrosoglutathione (GSNO). The GSNO decomposition - •NO release was evaluated by UV-VIS spectroscopy and Griess assay. The H2S donor Na2S was used.

Inhibitory effect of glybenclamide on mitochondrial chloride channels from rat heart.

Glybenclamide is used as a pharmacological tool in studies of mitochondrial functions supposing its main role to block ATP-dependent potassium (KATP) channel. The aim of this study was to test whether glybenclamide might interact with the mitochondrial chloride channels. Mitochondrial membranes, isolated from rat heart muscle, were incorporated into lipid bilayer membrane and single chloride channel currents were measured in 250/50 mM KCl cis/trans solutions.

The potassium channel opener CGS7184 activates Ca²⁺ release from the endoplasmic reticulum.

CGS7184 (ethyl 1-[[(4-chlorophenyl)amino]oxo]-2-hydroxy-6-trifluoromethyl-1H-indole-3-carboxylate) is a synthetic large-conductance Ca(2+)-activated potassium (BK(Ca)) channel opener. The existing literature suggests that potassium channels are involved in cardioprotection, particularly during ischemia-reperfusion events. However, the cellular mechanisms mediating the effects of CGS7184 remain unclear.

The aqueous garlic, onion and leek extracts release nitric oxide from S-nitrosoglutathione and prolong relaxation of aortic rings.

Garlic, onion and leek have beneficial effects in treatment of numerous health disorders. The aim of the present study was to investigate underlying molecular mechanisms. To test the potency of the aqueous garlic, onion and leek extracts to release NO from GSNO we have measured NO oxidation product, NO(2)-, by the Griess reagent method.

On the involvement of H2S in nitroso signaling and other mechanisms of H2S action.

Both endogenously produced and exogenously administered H2S exert numerous biological effects. However, the molecular mechanisms underlying these effects are not fully understood. This review surveys the biological effects of H2S and summarizes the molecular mechanisms of H2S action.

The hypothesis of the main role of H2S in coupled sulphide-nitroso signalling pathway.

As a part of the nitroso signalling pathway, nitroso-compounds serve as stores and carriers of NO; as part of the sulphide signalling pathway, bound sulfane-sulphur compounds serve as stores and carriers of H2S. Here we hypothesise a coupled sulphide-nitroso signalling pathway, in which H2S plays a main role. H2S releases NO from the endogenous S-nitroso-compounds nitroso-cysteine, nitroso-acetylcysteine and nitroso-albumin.

Modulation of intracellular chloride channels by ATP and Mg2+.

We report the effects of ATP and Mg2+ on the activity of intracellular chloride channels. Mitochondrial and lysosomal membrane vesicles isolated from rat hearts were incorporated into bilayer lipid membranes, and single chloride channel currents were measured. The observed chloride channels (n=112) possessed a wide variation in single channel parameters and sensitivities to ATP.

Mitochondrial chloride channels--What are they for?

This minireview focuses on observation of the properties, functional significance, and modulation of single chloride channels in the mitochondrial inner membrane using two electrophysiological methods--the patch-clamp and bilayer lipid membrane methods. Measurements of parameters such as conductance, Cl(-)/K(+) selectivity, voltage or pH dependence as well as their modulation by endogenous and exogenous compounds using individual mitochondrial chloride channels result in an unexpectedly wide range of values. This paper discusses the origin of this wide variety of channel parameters and the possible involvement of these channels in mitochondrial membrane potential oscillations, apoptosis, carrier function, and mitochondrial fusion and fission.

Lipids modulate H(2)S/HS(-) induced NO release from S-nitrosoglutathione.

Recently we observed that a gas messenger H(2)S/HS(-) released NO from S-nitrosoglutathione (Ondrias et al., Pflugers Arch. 457 (2008) 271-279).

The cardiac ryanodine receptor: looking for anomalies in permeation properties.

Anomalies in the permeation properties of the cardiac RyR channel reconstituted into bilayer lipid membranes were investigated systematically. We tested the presence of the anomalous mole fraction effect (AMFE) for the ion conductance and the reversal potential with varying mole fractions of two permeant ions, while the total ion concentration was lower, as in previous studies, to avoid the masking effect of the channel pore saturation with ions. Mixtures of Ba(2+) with other divalents (Ca(2+), Sr(2+)), of Ca(2+) with monovalents (Li(+), Cs(+)), and of Na(+) with other monovalents (Cs(+), Li(+)) were used.

Inhibition of anion channels derived from mitochondrial membranes of the rat heart by stilbene disulfonate--DIDS.

The objective of this work was to characterize in more detail the inhibition effect of diisothiocyanatostilbene-2',2-disulfonic acid (DIDS) on anion channels isolated from the rat heart mitochondria. The channels reconstituted into a planar lipid membrane displayed limited powers of discrimination between anions and cations and the ion conductance measured under asymmetric (250/50 mM KCl, cis/trans) and symmetric (150 mM KCl) conditions was approximately 100 pS. DIDS caused a dramatic decrease in the channel activity (IC(50) = 11.