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

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

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.

Molecular dissection of a basic COOH-terminal domain of Cx32 that inhibits gap junction gating sensitivity

1998 ◽  
Vol 275 (5) ◽  
pp. C1384-C1390 ◽  
Author(s):  
Xiao Guang Wang ◽  
Camillo Peracchia
Keyword(s):  
Gap Junction ◽  
Electrostatic Interactions ◽  
Xenopus Oocytes ◽  
Voltage Sensitivity ◽  
Wild Type ◽  
Cytoplasmic Loop ◽  
Terminal Domain ◽  
Gap Junction Channel ◽  
Chemical Gating

Connexin32 (Cx32) mutants were studied by double voltage clamp in Xenopus oocytes to determine the role of basic COOH-terminal residues in gap junction channel gating by CO2 and transjunctional voltage. Replacement of five arginines with N (5R/N) or T residues in the initial COOH-terminal domain (CT1) of Cx32 enhanced CO2 sensitivity. The positive charge, rather than the R residue per se, is responsible for the inhibitory role of CT1, because mutants replacing the five R residues with K (5R/K) or H (5R/H) displayed CO2 sensitivity comparable to that of wild-type Cx32. Mutants replacing R with N residues four at a time (4R/N) showed that CO2 sensitivity is strongly inhibited by R215 and mildly by R219, whereas R220, R223, and R224 may slightly increase sensitivity. Neither the 5R/N nor the 4R/N mutants differed in voltage sensitivity from wild-type Cx32. The possibility that inhibition of gating sensitivity results from electrostatic interactions between CT1 and the cytoplasmic loop is discussed as part of a model that envisions the cytoplasmic loop of Cx32 as a key element of chemical gating.

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 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 Gating of connexin 43 gap junctions by a cytoplasmic loop calmodulin binding domain

2012 ◽  
Vol 302 (10) ◽  
pp. C1548-C1556 ◽  
Author(s):  
Qin Xu ◽  
Richard F. Kopp ◽  
Yanyi Chen ◽  
Jenny J. Yang ◽  
Michael W. Roe ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Connexin 43 ◽  
Binding Domain ◽  
Cytoplasmic Loop ◽  
Inhibitory Peptide ◽  
Open Probability ◽  
Calmodulin Binding ◽  
Gap Junction Channel ◽  
Whole Cell Patch Clamp

Calmodulin (CaM) binding sites were recently identified on the cytoplasmic loop (CL) of at least three α-subfamily connexins (Cx43, Cx44, Cx50), while Cx40 does not have this putative CaM binding domain. The purpose of this study was to examine the functional relevance of the putative Cx43 CaM binding site on the Ca2+-dependent regulation of gap junction proteins formed by Cx43 and Cx40. Dual whole cell patch-clamp experiments were performed on stable murine Neuro-2a cells expressing Cx43 or Cx40. Addition of ionomycin to increase external Ca2+ influx reduced Cx43 gap junction conductance (Gj) by 95%, while increasing cytosolic Ca2+ concentration threefold. By contrast, Cx40 Gj declined by <20%. The Ca2+-induced decline in Cx43 Gj was prevented by pretreatment with calmidazolium or reversed by the addition of 10 mM EGTA to Ca2+-free extracellular solution, if Ca2+ chelation was commenced before complete uncoupling, after which gj was only 60% recoverable. The Cx43 CL136–158 mimetic peptide, but not the scrambled control peptide, or Ca2+/CaM-dependent kinase II 290–309 inhibitory peptide also prevented the Ca2+/CaM-dependent decline of Cx43 Gj. Cx43 gap junction channel open probability decreased to zero without reductions in the current amplitudes during external Ca2+/ionomycin perfusion. We conclude that Cx43 gap junctions are gated closed by a Ca2+/CaM-dependent mechanism involving the carboxyl-terminal quarter of the connexin CL domain. This study provides the first evidence of intrinsic differences in the Ca2+ regulatory properties of Cx43 and Cx40.

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.

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.

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.

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