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Mitochondria contain a potassium specific channel (mitoKATP channel) sensitive to ATP and antidiabetic sulfonylureas. The mitochondrial Katp channel plays an important role in the mitochondrial volume control and in regulation of the components of protonmotive force. This minireview describes the properties and current hypotheses concerning the function of mitoKATP channel.
We describe a new factor in the recovery from inactivation in the ball and chain model. We propose a model in which the tension from the chain may help pull the ball away from its binding site, reducing the duration of the inactivation period. A corresponding model was built and analysed.
The whole-cell patch clamp technique was used to record potassium currents in in vitro differentiating myoblasts isolated from healthy and myotonic dystrophy type 1 (DM1) foetuses carrying 2000 CTG repeats. The fusion of the DM1 myoblasts was reduced in comparison to that of the control cells. The dystrophic muscle cells expressed less voltage-activated K+ (delayed rectifier and non-inactivating delayed rectifier) and inward rectifier channels than the age-matched control cells. However, the resting membrane potential was not significantly different between the control and the DM1 cells. After four days in a differentiation medium, the dystrophic cells expressed the fast-inactivating transient outward K+ channels, which were not observed in healthy cells. We suggest that the low level of potassium currents measured in differentiated DM1 cells could be related to their impaired fusion.
The mitochondrial ATP-sensitive K+ (mitoKATP) channel was discovered more than a decade ago. Since then, several pharmacological studies have identified agents that target this channel some of which selectively target mitoKATP. These and other studies have also suggested that mitoKATP plays a key role in the process of ischemic preconditioning (IPC) and prevention of apoptosis. The mechanism by which mitoKATP exerts its protective effects is unclear, however, changes in mitochondrial Ca2+ uptake and levels of reactive oxygen species, and mitochondrial matrix swelling are believed to be involved. Despite major advances, several important issues re­garding mitoKATP remain unanswered. These questions include, but are not limited to: the molecular structure of mitoKATP, the downstream and upstream mechanisms that leads to IPC and cell death, and the pharmacological profile of the channel. This review attempts to provide an up-to-date overview of the role of mitoKATP in cardioprotection.
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The inhibitory effect of copper ions on lymphocyte Kv1.3 potassium channels

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We applied the whole-cell patch-clamp technique to study the inhibitory effect of copper ions (Cu) on the activity of Kv1.3 channels expressed in human lymphocytes. Application of Cu reversibly inhibited the currents to about 10% of the control value in a concentration-dependent manner with the half blocking concentration of 5.28±0.5 µM and the Hill's coefficient of 3.83±0.18. The inhibitory effect was saturated at 10 µM concentration. The inhibition was time-dependent and it was correlated in time with a significant slowing of the current activation rate. In contrast the voltage dependence of activation was not changed by Cu as well as the inativation kinetics. The inhibitory effect of Cu was voltage-independent. It was also unaffected by changing the extracellular pH in the range from 6.4 to 8.4, raising the extracellular potassium concentration to 150 mM and by changing the holding potential from -90 to -60 mV. The inhibitiory effect of Cu was not changed in the presence of an equivalent concentration of Zn. Altogether, obtained data suggest that Cu inhibits Kv1.3 channels by a different mechanism than Zn and that Cu and Zn act on different binding sites. The inhibitory effect of Cu was probably due to a specific binding of Cu on binding sites on the channels. Possible physiological significance of the Cu-induced inhibition of Kv1.3 channels is discussed.
We applied the whole-cell patch-clamp technique to study the influence of zinc ions (Zn2+) and extracellular protons at acidic pH (pHo) on voltage-gated potassium currents in cultured rat hippocampal neurons. The first goal of the study was to estimate whether Kv1.3 currents significantly contributed to voltage-gated potassium currents in examined cells. Then, the influence of both ions on the activity of other voltage-gated potassium currents in the neurons was examined. We examined both the total current and the delayed - rectifier component. Results obtained in both cases were not significantly different from each other. Available data argued against any significant contribution of Kv1.3 currents to the recorded currents. Nevertheless, application of Zn2+ in the concentration range from 100 µM to 5 mM reversibly modulated the recorded currents. The activation midpoint was shifted by about 40 mV (total current) and 30 mV (delayed-rectifier current) towards positive membrane potentials and the activation kinetics were slowed significantly (2 - 3 fold) upon application of Zn2+. The inactivation midpoint was also shifted towards positive membrane potentials, but less significantly (about 14 mV). The current amplitudes were reduced in a concentration-dependent manner to about 0.5 of the control value. The effects of Zn2+ were saturated at the concentration of 1 mM. Raising extracellular proton concentration by lowering the pHo from 7.35 to 6.4 did not affect significantly the currents. Possible mechanisms underlying the observed phenomena and their possible physiological significance are discussed.
The ion current through individual etched ion tracks (diameter ≈50 nm, length ≈12 µm) in a poly (ethylene terephthalate) membrane is recorded at pH 7 as function of applied voltage (-5V to +5V) across the membrane. With increasing voltage, the ion current changes abruptly from random oscillations to structured fluctuations. The power spectrum and the generalized entropy of the recorded current reminds of the potassium channel of a locust muscle cell.
The aim of this study was to investigate whether apamin-sensitive K+ channels play a role in the NO induced relaxation of the human pregnant myometrium. Concentration-response curves for sodium nitroprusside (SNP) (10-9 – 10-4 M) were constructed in the absence and presence of 10-8 M apamin and 10-7 M charybdotoxin (CTX). Preincubation with apamin resulted in a significant attenuation of the relaxation caused by SNP, while pre-treatment with CTX insignificantly decreased the SNP induced relaxation. Our findings suggest that apamin-sensitive K+ channels exist in the human pregnant myometrium and play a role in modulation of the myometrium response to NO donors.
In the present study we applied the whole-cell patch-clamp technique to study the influence of extracellular pH (pHo) on the modulatory effect exerted by zinc ions (Zn2+) on voltage-gated potassium channels Kv1.3 expressed in human lymphocytes. Obtained data provide evidence that lowering of pHo from the 7.35 to 6.4 slowed significantly the current activation rate, shifted the activation midpoint by about 16 mV towards positive membrane potentials and reduced the current amplitude to about 0.55 of the control value. In contrast, raising the pHo from 7.35 to 8.4 did not affect significantly the activation midpoint and current amplitude. Application of Zn2+ in the concentration range from 100 µM to 1 mM at pHo=6.4 slowed additionally the activation rate, shifted the activation midpoint by about 20 mV towards positive membrane potentials and reduced the current amplitude in a concentration-dependent manner. The total effect exerted by Zn2+ and protons at pHo = 6.4 was more significant than the effect exerted by Zn alone. Both the magnitude of the shift and the degree of current inhibition by Zn2+ were independent on pHo in the range from 6.4 to 8.4. The data might suggest that the effects exerted by protons and zinc ions occur independently on each other and probably involve different mechanisms. Changing the holding potential from -90 mV to -60 mV at pHo=7.35 abolished the Zn2+-induced inhibition of the current amplitudes at concentrations below 300 µM. At pHo=6.4 the total inhibition caused by Zn2+ and protons was also diminished, however, a significant reduction was observed at 100 µM concentration. In contrast, changing the holding potential did not change the Zn2+- and proton-induced shift of the activation midpoint. Altogether, obtained data suggest that extracellular protons exert the modulatory effects that are additive to the effects exerted by Zn2+ on the channels. Possible physiological significance of these additive effects is discussed.
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