Calmodulin-connexin colocolization and direct role of calmodulin in gap junction channel gating

2000 ◽  
Vol 32 (3) ◽  
pp. 132-133
Author(s):  
A. Sotkis ◽  
X. G. Wang ◽  
L. L. Peracchia ◽  
A. J. Persechini ◽  
C. Peracchia
Keyword(s):  
Gap Junction ◽  
Channel Gating ◽  
Direct Role ◽  
Gap Junction Channel

scholarly journals Gap Junction Channelopathies and Calmodulinopathies. Do Disease-Causing Calmodulin Mutants Affect Direct Cell–Cell Communication?

2021 ◽  
Vol 22 (17) ◽  
pp. 9169
Author(s):  
Camillo Peracchia
Keyword(s):  
Gap Junction ◽  
Genetic Diseases ◽  
Channel Gating ◽  
Cell Communication ◽  
Potential Effect ◽  
Gap Junction Channel ◽  
Direct Cell ◽  
Connexin Genes ◽  
Cell Cell

The cloning of connexins cDNA opened the way to the field of gap junction channelopathies. Thus far, at least 35 genetic diseases, resulting from mutations of 11 different connexin genes, are known to cause numerous structural and functional defects in the central and peripheral nervous system as well as in the heart, skin, eyes, teeth, ears, bone, hair, nails and lymphatic system. While all of these diseases are due to connexin mutations, minimal attention has been paid to the potential diseases of cell–cell communication caused by mutations of Cx-associated molecules. An important Cx accessory protein is calmodulin (CaM), which is the major regulator of gap junction channel gating and a molecule relevant to gap junction formation. Recently, diseases caused by CaM mutations (calmodulinopathies) have been identified, but thus far calmodulinopathy studies have not considered the potential effect of CaM mutations on gap junction function. The major goal of this review is to raise awareness on the likely role of CaM mutations in defects of gap junction mediated cell communication. Our studies have demonstrated that certain CaM mutants affect gap junction channel gating or expression, so it would not be surprising to learn that CaM mutations known to cause diseases also affect cell communication mediated by gap junction channels.

scholarly journals Calmodulin-Cork Model of Gap Junction Channel Gating—One Molecule, Two Mechanisms

2020 ◽  
Vol 21 (14) ◽  
pp. 4938 ◽  
Author(s):  
Camillo Peracchia
Keyword(s):  
Single Channel ◽  
Channel Gating ◽  
Cytosolic Calcium ◽  
Direct Role ◽  
Gating Model ◽  
Gap Junction Channel ◽  
Ef Hand ◽  
Chemical Gating ◽  
Terminal Pair

The Calmodulin-Cork gating model is based on evidence for the direct role of calmodulin (CaM) in channel gating. Indeed, chemical gating of cell-to-cell channels is sensitive to nanomolar cytosolic calcium concentrations [Ca2+]i. Calmodulin inhibitors and inhibition of CaM expression prevent chemical gating. CaMCC, a CaM mutant with higher Ca2+-sensitivity greatly increases chemical gating sensitivity (in CaMCC the NH2-terminal EF-hand pair (res. 9–76) is replaced by the COOH-terminal pair (res. 82–148). Calmodulin colocalizes with connexins. Connexins have high-affinity CaM binding sites. Several connexin mutants paired to wild-type connexins have a high gating sensitivity that is eliminated by inhibition of CaM expression. Repeated transjunctional voltage (Vj) pulses slowly and progressively close a large number of channels by the chemical/slow gate (CaM lobe). At the single-channel level, the chemical/slow gate closes and opens slowly with on-off fluctuations. The model proposes two types of CaM-driven gating: “Ca-CaM-Cork” and “CaM-Cork”. In the first, gating involves Ca2+-induced CaM-activation. In the second, gating takes place without [Ca2+]i rise. The Ca-CaM-Cork gating is only reversed by a return of [Ca2+]i to resting values, while the CaM-Cork gating is reversed by Vj positive at the gated side.

Chimeric evidence for a role of the connexin cytoplasmic loop in gap junction channel gating

1996 ◽  
Vol 431 (6) ◽  
pp. 844-852 ◽  
Author(s):  
Xiaoguang Wang ◽  
Liqiong Li ◽  
Lillian L. Peracchia ◽  
Camillo Peracchia
Keyword(s):  
Gap Junction ◽  
Channel Gating ◽  
Cytoplasmic Loop ◽  
Gap Junction Channel

Calmodulin Colocalizes with Connexins and Plays a Direct Role in Gap Junction Channel Gating

2001 ◽  
Vol 8 (4-6) ◽  
pp. 277-281 ◽  
Author(s):  
Anna Sotkis ◽  
Xiao G. Wang ◽  
Thomas Yasumura ◽  
Lillian L. Peracchia ◽  
Anthony Persechini ◽  
...  
Keyword(s):  
Gap Junction ◽  
Channel Gating ◽  
Direct Role ◽  
Gap Junction Channel

Chimeric evidence for a role of the connexin cytoplasmic loop in gap junction channel gating

1996 ◽  
Vol 431 (S6) ◽  
pp. 844-852 ◽  
Author(s):  
Xiaoguang Wang ◽  
Liqiong Li ◽  
Lillian L. Peracchia ◽  
Camillo Peracchia
Keyword(s):  
Gap Junction ◽  
Channel Gating ◽  
Cytoplasmic Loop ◽  
Gap Junction Channel

scholarly journals Gap junction channel gating

2004 ◽  
Vol 1662 (1-2) ◽  
pp. 42-60 ◽  
Author(s):  
Feliksas F Bukauskas ◽  
Vytas K Verselis
Keyword(s):  
Gap Junction ◽  
Channel Gating ◽  
Gap Junction Channel

scholarly journals Role of Gap Junctions and Hemichannels in Parasitic Infections

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
José Luis Vega ◽  
Mario Subiabre ◽  
Felipe Figueroa ◽  
Kurt Alex Schalper ◽  
Luis Osorio ◽  
...  
Keyword(s):  
Gap Junction ◽  
Viral Infections ◽  
Cellular Communication ◽  
Parasitic Infections ◽  
Pathological State ◽  
Channel Changes ◽  
Gap Junction Channels ◽  
Gap Junction Channel ◽  
Relevant Role

In vertebrates, connexins (Cxs) and pannexins (Panxs) are proteins that form gap junction channels and/or hemichannels located at cell-cell interfaces and cell surface, respectively. Similar channel types are formed by innexins in invertebrate cells. These channels serve as pathways for cellular communication that coordinate diverse physiologic processes. However, it is known that many acquired and inherited diseases deregulate Cx and/or Panx channels, condition that frequently worsens the pathological state of vertebrates. Recent evidences suggest that Cx and/or Panx hemichannels play a relevant role in bacterial and viral infections. Nonetheless, little is known about the role of Cx- and Panx-based channels in parasitic infections of vertebrates. In this review, available data on changes in Cx and gap junction channel changes induced by parasitic infections are summarized. Additionally, we describe recent findings that suggest possible roles of hemichannels in parasitic infections. Finally, the possibility of new therapeutic designs based on hemichannel blokers is presented.

Modulation of gap-junction channel gating at zebrafish retinal electrical synapses

1994 ◽  
Vol 72 (5) ◽  
pp. 2257-2268 ◽  
Author(s):  
D. G. McMahon ◽  
D. R. Brown
Keyword(s):  
Gap Junction ◽  
Horizontal Cell ◽  
Channel Gating ◽  
Horizontal Cells ◽  
General Mechanism ◽  
Spatial Integration ◽  
Open Probability ◽  
Electrical Synapses ◽  
Gap Junction Channels ◽  
Gap Junction Channel

1. Transmission at electrical synapses is modulated by a variety of physiological signals, and this modulation is a potentially general mechanism for regulating signal integration in neural circuits and networks. In the outer plexiform layer of the retina, modulation of horizontal-cell electrical coupling by dopamine alters the extent of spatial integration in the horizontal-cell network. By analyzing the activity of individual gap-junction channels in low-conductance electrical synapses of zebrafish retinal horizontal cells, we have defined the properties of these synaptic ion channels and characterized the functional changes in them during modulation of horizontal-cell electrical synapses. 2. Zebrafish horizontal-cell gap-junction channels have a unitary conductance of 50–60 pS and exhibit open times of several tens of milliseconds. The kinetic process of channel closure is best described by the sum of two rate constants. 3. Dopamine, and its agonist, (+/-)-6,7-dihydroxy-2-amino-tetralin (ADTN), modulates electrical synaptic transmission between horizontal cells predominantly by affecting channel-gating kinetics. These agents reduced the open probability of gap-junction channels two- to threefold by reducing both the duration and frequency of channel openings. Both time constants for channel open duration were reduced, whereas the duration of shut periods was increased. Similar changes in open-time kinetics were observed in power spectra of higher conductance gap junctions. 4. These results provide a description of rapid electrical synaptic modulation at the single channel level. The description should be useful in understanding the mechanisms of plasticity at these synapses throughout the vertebrate central nervous system.

Structure of the Ductin Channel

1998 ◽  
Vol 18 (6) ◽  
pp. 287-297 ◽  
Author(s):  
Malcolm E. Finbow ◽  
John D. Pitts
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Cell Movement ◽  
Large Family ◽  
Structural Data ◽  
Proton Pumps ◽  
Gap Junction Channel ◽  
Essential Components ◽  
Resolution Model

Gap junctions appear to be essential components of metazoan animals providing a means of direct means of communication between neighboring cells. They are sieve-like structures which allow cell–cell movement of cytosolic solutes below 1000 MW. The major role of gap junctions would appear to be homeostatic giving rise to groups of cells which act as functional units. Ductin is the major core component of gap junctions and recent structural data shows it to be a four alpha-helical bundle which fits particularly well into a low resolution model of the gap junction channel. Ductin is also the main membrane component of the vacuolar H+-ATPase that is found in all eukaryotes and it seems likely that the gap junction channel first evolved as a housing for the rotating spindle of these proton pumps. Because ductin protrudes little from the membrane, other proteins are required to bring cell surfaces close enough together to form gap junctions. Such proteins may include connexins, a large family of proteins found in vertebrates.

scholarly journals Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

2014 ◽  
Vol 21 (8) ◽  
pp. 1042-1052 ◽  
Author(s):  
Janos Magyar ◽  
Tamas Banyasz ◽  
Norbert Szentandrassy ◽  
Kornel Kistamas ◽  
Peter Nanasi ◽  
...  
Keyword(s):  
Action Potential ◽  
Gap Junction ◽  
Gap Junction Channel ◽  
Action Potential Repolarization
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