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Handbook of Experimental Pharmacology 2017This chapter provides a critical overview of the available literature on the pharmacology of mitochondrial potassium channels. In the first part, the reader is... (Review)
Review
This chapter provides a critical overview of the available literature on the pharmacology of mitochondrial potassium channels. In the first part, the reader is introduced to the topic, and eight known protein contributors to the potassium permeability of the inner mitochondrial membrane are presented. The main part of this chapter describes the basic characteristics of each channel type mentioned in the introduction. However, the most important and valuable information included in this chapter concerns the pharmacology of mitochondrial potassium channels. Several available channel modulators are critically evaluated and rated by suitability for research use. The last figure of this chapter shows the results of this evaluation at a glance. Thus, this chapter can be very useful for beginners in this field. It is intended to be a time- and resource-saving guide for those searching for proper modulators of mitochondrial potassium channels.
Topics: Animals; Humans; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Mitochondria; Potassium Channels; Potassium Channels, Voltage-Gated
PubMed: 27838853
DOI: 10.1007/164_2016_79 -
Hearing Research Jun 2007Potassium channels play a critical role in defining the electrophysiological properties accounting for the unique response patterns of auditory neurons. Serial analysis... (Comparative Study)
Comparative Study
Potassium channels play a critical role in defining the electrophysiological properties accounting for the unique response patterns of auditory neurons. Serial analysis of gene expression (SAGE), microarrays, RT-PCR, and real-time RT-PCR were used to generate a broad profile of potassium channel expression in the rat cochlear nucleus. This study identified mRNAs for 51 different potassium channel subunits or channel interacting proteins. The relative expression levels of 27 of these transcripts among the AVCN, PVCN, and DCN were determined by real-time RT-PCR. Four potassium channel transcripts showed substantial levels of differential expression. Kcnc2 was expressed more than 15-fold higher in the DCN as compared to AVCN and PVCN. In contrast, Kcnj13 had an approximate 10-fold higher expression in AVCN and PVCN than in DCN. Two subunits that modify the activity of other channels were inversely expressed between ventral and dorsal divisions. Kcns1 was over 15-fold higher in DCN than AVCN or PVCN, while Kcns3 was about 25-fold higher in AVCN than in DCN. The expression patterns of potassium channels in the subdivisions of the cochlear nucleus provide a basis for understanding the electrophysiological mechanisms which sub-serve central auditory processing and provide targets for further investigations into neural plastic changes that occur with hearing loss.
Topics: Animals; Cochlear Nucleus; Female; Gene Expression; Gene Expression Profiling; Oligonucleotide Array Sequence Analysis; Potassium Channels; Potassium Channels, Inwardly Rectifying; Potassium Channels, Voltage-Gated; RNA, Messenger; Rats; Rats, Inbred BN; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Shaw Potassium Channels
PubMed: 17346910
DOI: 10.1016/j.heares.2007.01.024 -
Molecules (Basel, Switzerland) Jan 2022Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and... (Review)
Review
Mitochondrial potassium channels control potassium influx into the mitochondrial matrix and thus regulate mitochondrial membrane potential, volume, respiration, and synthesis of reactive oxygen species (ROS). It has been found that pharmacological activation of mitochondrial potassium channels during ischemia/reperfusion (I/R) injury activates cytoprotective mechanisms resulting in increased cell survival. In cancer cells, the inhibition of these channels leads to increased cell death. Therefore, mitochondrial potassium channels are intriguing targets for the development of new pharmacological strategies. In most cases, however, the substances that modulate the mitochondrial potassium channels have a few alternative targets in the cell. This may result in unexpected or unwanted effects induced by these compounds. In our review, we briefly present the various classes of mitochondrial potassium (mitoK) channels and describe the chemical compounds that modulate their activity. We also describe examples of the multidirectional activity of the activators and inhibitors of mitochondrial potassium channels.
Topics: Adenosine Triphosphate; Animals; Calcium; Humans; Ion Channel Gating; Mitochondrial Membrane Transport Proteins; Potassium; Potassium Channel Blockers; Potassium Channels
PubMed: 35011530
DOI: 10.3390/molecules27010299 -
Cardiovascular Drugs and Therapy Mar 1995Potassium-channel openers or activators have been introduced as a new class of antihypertensive and antianginal agents that act by increasing membrane conductance to... (Review)
Review
Potassium-channel openers or activators have been introduced as a new class of antihypertensive and antianginal agents that act by increasing membrane conductance to potassium, mainly through augmentation of the ATP-sensitive potassium current. Recent in vitro studies have shown that K(+)-channel openers exert concentration-dependent effects on cardiac electrophysiology. A shortening of the cardiac action potential by acceleration of repolarization has been reported in multicellular preparations as well as in isolated myocytes. However, drug concentrations that affect the action potential duration of myocardial cells are considerably higher (10- to 100-fold) than those needed for effects on vascular smooth muscle cells. Studies in which mostly high concentrations of K(+)-channel openers were used have demonstrated that these drugs may accelerate automaticity and may promote reentrant activity. Particular interest has focused on the question whether opening of potassium channels may be potentially arrhythmogenic in the setting of acute myocardial ischemia. On the other hand, recent studies have shown that K(+)-channel openers are effective in suppressing polymorphic ventricular tachyarrhythmias induced by early afterdepolarizations and triggered activity in vivo. The clinical relevance of these experimental studies to the clinical situation is still unclear. Some K(+)-channel openers have been shown to produce electrocardiographic T-wave changes in patients in whom their effectiveness as antihypertensives was tested. However, this effect was not associated with adverse effects and has not been demonstrated for all compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Anti-Arrhythmia Agents; Electrophysiology; Humans; Potassium Channels
PubMed: 7647023
DOI: 10.1007/BF00878466 -
Cardiovascular Drugs and Therapy Aug 1993During acute myocardial ischemia, passage of potassium ions across the sarcolemma to the extracellular space is a well-established phenomenon. A recent hypothesis is... (Review)
Review
During acute myocardial ischemia, passage of potassium ions across the sarcolemma to the extracellular space is a well-established phenomenon. A recent hypothesis is that the ATP-dependent potassium channel plays a role in contributing to the potassium loss. As the potassium loss starts while the overall level of ATP is still relatively high, and as the channel is inhibited by rather low concentrations of ATP, the question arises as to how the channel is opened. Among the proposals are that, in addition to the total concentration of ATP, there is modulation of the regulation by its breakdown products, such as ADP and adenosine. Alternatively, or in addition, breakdown products of anaerobic glycolysis, such as lactate and protons, may also play a role. Extracellular acidosis may help to activate the channel, and internal lactate accumulation may have a similar effect. In certain circumstances there is evidence that ATP produced by glycolysis plays a significant role in the control of potassium channel activity. The concept of subsarcolemmal ATP is another explanation for the activation of the channel at relatively high ATP concentrations. Potassium channel closing drugs, such as glibenclamide, may prolong the action potential duration (shortened by ischemia) and thereby decrease the incidence of early ventricular arrhythmias. This same category of drugs may reduce early potassium loss from the ischemic tissue, thereby lessening the potentially protective effect of the external accumulation of potassium on the ischemic zone, the so-called local cardioplegic effect. Conversely, drugs of the potassium channel activating group are likely to have opposite effects on these arrhythmias and on myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adenosine Triphosphate; Animals; Glyburide; Myocardial Ischemia; Potassium Channels
PubMed: 8251420
DOI: 10.1007/BF00877615 -
Progress in Drug Research. Fortschritte... 1997
Review
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Potassium Channels
PubMed: 9388385
DOI: 10.1007/978-3-0348-8863-9_3 -
FEBS Letters Nov 2003The atomic structures of K+ channels have added a new dimension to our understanding of K+ channel function. I will briefly review how structures have influenced our... (Review)
Review
The atomic structures of K+ channels have added a new dimension to our understanding of K+ channel function. I will briefly review how structures have influenced our views on ion conduction, gating of the pore, and voltage sensing.
Topics: Amino Acid Sequence; Bacterial Proteins; Ion Channel Gating; Ion Transport; Membrane Potentials; Models, Molecular; Molecular Sequence Data; Potassium Channels; Protein Conformation; Sequence Homology, Amino Acid
PubMed: 14630320
DOI: 10.1016/s0014-5793(03)01104-9 -
The Journal of Physiology Jun 2015The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the... (Review)
Review
The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane.
Topics: Cell Membrane; Humans; Ion Channel Gating; Potassium Channels
PubMed: 25833254
DOI: 10.1113/JP270025 -
Current Topics in Membranes 2014At normal body temperature, the two-pore potassium channels TREK-1 (K2P2.1/KCNK2), TREK-2 (K2P10.1/KCNK10), and TRAAK (K2P4.1/KCNK2) regulate cellular excitability by... (Review)
Review
At normal body temperature, the two-pore potassium channels TREK-1 (K2P2.1/KCNK2), TREK-2 (K2P10.1/KCNK10), and TRAAK (K2P4.1/KCNK2) regulate cellular excitability by providing voltage-independent leak of potassium. Heat dramatically potentiates K2P channel activity and further affects excitation. This review focuses on the current understanding of the physiological role of heat-activated K2P current, and discusses the molecular mechanism of temperature gating in TREK-1, TREK-2, and TRAAK.
Topics: Animals; Ion Channel Gating; Mechanical Phenomena; Potassium Channels; Thermosensing
PubMed: 25366235
DOI: 10.1016/B978-0-12-800181-3.00005-1 -
The Journal of Neuroscience : the... Dec 1988A number of mutations have been shown to affect potassium channels in Drosophila muscle. Single-channel analysis of the effects of mutations will prove a powerful...
A number of mutations have been shown to affect potassium channels in Drosophila muscle. Single-channel analysis of the effects of mutations will prove a powerful approach for studying the molecular mechanisms of ion channel gating. As an initial step towards studying the effects of mutations at the single-channel level, we have characterized wild-type potassium channels in cultured embryonic myotubes using whole-cell, cell-attached, inside-out, and outside-out configurations of the patch-clamp technique. The myotubes differentiate in vitro from primary cultures of late-gastrula stage embryos of Drosophila. The whole-cell outward currents develop in a characteristic sequence. At 8 hr after plating a small delayed outward current is present. Between 10 and 12 hr after plating an A-type outward current develops, followed, between 13 and 16 hr, by a large increase in the delayed current. The A-type current is absent at all developmental stages in myotubes homozygous for the mutant ShKS133. At least 4 different types of potassium channels contribute to the whole-cell outward currents: a fast transient 14 pS A-type potassium channel (A1), a slowly inactivating 14 pS potassium channel (KD), a 40 pS potassium channel that does not inactivate during voltage pulses up to 2.4 sec in duration (KO), and a 90 pS potassium channel that is strongly activated by membrane stretch (KST). Channels indistinguishable from the KD and KST channels were also observed in patch-clamp studies on larval body wall muscle fibers. A1 channels were also present in intact dorsal longitudinal flight muscles. The A1 channel underlies the rapidly inactivating component of the whole-cell current. It inactivates with a similar time course and voltage dependence to the A-current and is similarly blocked by 5 mM 4-aminopyridine. The KD channel underlies a large fraction of the delayed component of the whole-cell current. Ensemble averages of single KD channels inactivate with the same time course as the delayed current. The KO channel represents a smaller fraction of the whole-cell delayed outward current. Its increase in open probability with voltage is due primarily to a voltage dependence of its closed times. The KST channel is voltage and calcium independent and would therefore only contribute to the leak whole-cell current.
Topics: Animals; Drosophila; Electrophysiology; Larva; Muscles; Potassium Channels; Pupa
PubMed: 3199204
DOI: 10.1523/JNEUROSCI.08-12-04765.1988