Lack of CMBK channels renders the heart more susceptible to ischemia/reperfusion injury, whereas the pathological events elicited by ischemia/reperfusion do not involve BK in vascular smooth muscle cells. BK seems to permit the protective effects triggered by cinaciguat, riociguat, and different phosphodiesterase-5 inhibitors and beneficial actions of ischemic preconditioning and ischemic postconditioning by a mechanism stemming primarily from cardiomyocytes. This study establishes mitochondrial CMBK channels as a promising target for limiting acute cardiac damage and adverse long-term events that occur after myocardial infarction.

In this review, we summarize our knowledge about mitochondrial potassium channels, with a special focus on unanswered questions in this field. The following potassium channels have been well described in the inner mitochondrial membrane: ATP-regulated potassium channel, Ca(2+)-activated potassium channel, the voltage-gated Kv1.3 potassium channel, and the two-pore domain TASK-3 potassium channel. The primary functional roles of these channels include regulation of mitochondrial respiration and the alteration of membrane potential. Additionally, they modulate the mitochondrial matrix volume and the synthesis of reactive oxygen species by mitochondria. Mitochondrial potassium channels are believed to contribute to cytoprotection and cell death. In this paper, we discuss fundamental issues concerning mitochondrial potassium channels: their molecular identity, channel pharmacology and functional properties. Attention will be given to the current problems present in our understanding of the nature of mitochondrial potassium channels. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

Motile cilia have nine doublet microtubules, with hundreds of associated proteins that repeat in modules. Each module contains three radial spokes, which differ in their architecture, protein composition, and function. The conserved proteins FAP61 and FAP251 are crucial for the assembly and stable docking of RS3 and cilia motility.

Heptameric YggB is a mechanosensitive ion channel (MscS) from the inner membrane of Escherichia coli. We demonstrate, using the patch clamp technique, that cross-linking of the YggB C termini led to irreversible inhibition of the channel activities. Application of Ni 2؉ to the YggB-His 6 channels with the hexahistidine tags added to the ends of their C termini also resulted in a marked but reversible decrease of activities. Western blot revealed that YggB-His 6 oligomers are more stable in the presence of Ni 2؉ , providing evidence that Ni 2؉ is coordinated between C termini from different subunits of the channel. Intersubunit coordination of Ni 2؉ affecting channel activities occurred in the channel closed conformation and not in the open state. This may suggest that the C termini move apart upon channel opening and are involved in the channel activation. We propose that the as yet undefined C-terminal region may form a cytoplasmic gate of the channel. The results are discussed and interpreted based on the recently released quaternary structure of the channel. Mechanosensitive (MS)1 ion channels open upon membrane tension, and therefore they represent the simplest mechanosensors. MS channels have been implicated in many physiological processes from growth and cell volume regulation to hearing, blood pressure regulation, and pain sensation (reviewed in Ref. 1). Bacterial MS channels protect these cells against hypoosmotic shock. Two types of MS channels from the cytoplasmic membrane of Escherichia coli, MscL and MscS, play an essential role in the physiology of this bacterium, allowing the efflux of solutes from the cytoplasm when osmolarity of the external medium decreases (2-4). MscL, the large conductance MS channel, has been cloned (5), and a quaternary structure of its closed conformation has been determined (6). Based on this structure and the analysis of the channel gating, the open conformation has been predicted (7, 8) and experimentally confirmed (9, 10). Functional homologues of this channel have been found in other bacteria (11) and Archea (12), and structurally related protein from Neurospora has been also reported (13). The functional channel is a pentamer, and each subunit consists of two ␣-helical membrane-spanning domains TM1 and TM2 with both the C and N termini located in the cytoplasm (6). TM1s line the pore, and their hydrophobic residues form the primary, transmembrane gate (6, 14). It is postulated that there are two gates involved in the opening of the channel: the transmembrane and the cytoplasmic gates (7, 8) acting in accordance (15). The transmembrane gate is proposed to act as a pressure sensor, and upon application of pressure, this gate permits initial expansion of the channel without its full opening (7,8,10). It is proposed that the other, cytoplasmic gate, which allows full activation of the channel, is composed of five ␣-helical S1 segments of the cytoplasmic N termini being connected with TM1s via flexible linkers. According to the model, the applied pressure is transmitted to...

Mechanosensitive (MS) ion channels, with 560 pS conductance, opened transiently by rapid application of suction pulses to patches of E. coli protoplast membrane. The adaptation phase of the response was voltage-independent. Application of strong suction pulses, which were sufficient to cause saturation of the MS current, did not abolish the adaptation. Multiple-pulse experimental protocols revealed that once MS channels had fully adapted, they could be reactivated by a second suction pulse of similar amplitude, providing the time between pulses was long enough and suction had been released between pulses. Limited proteolysis (0.2 mg/ml pronase applied to the cytoplasmic side of the membrane patch) reduced the number of open channels without affecting the adaptation. Exposing patches to higher levels of pronase (1 mg/ml) removed responsiveness of the channel to suction and abolished adaptation consistent with disruption of the tension transmission mechanism responsible for activating the MS channel. Based on these data we discuss a mechanism for mechanosensitivity mediated by a cytoplasmic domain of the MS channel molecule or associated protein.