Pannexins and gap junction protein diversity

Shestopalov, Valery I.; Panchin, Yu. V.

doi:10.1007/s00018-007-7200-1

Cited by 162 publications

(158 citation statements)

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“…Hemichannels formed by connexins or pannexins possess permeability to molecules of up to 1,000 Da (10,22,23,63,70). We tested whether the ionomycin-induced pore formation might be due to hemichannels activation.…”

Section: Phospholipase C Inhibitors Blocked Ionomycin-induced Pore Fomentioning

confidence: 99%

Pharmacological properties of a pore induced by raising intracellular Ca²⁺

Faria¹,

Reis²,

Casabulho³

et al. 2009

American Journal of Physiology-Cell Physiology

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-Recent studies on the P2X 7 receptor in 2BH4 cells and peritoneal macrophages have demonstrated that the raise in intracellular Ca 2ϩ concentration induces a pore opening similar to P2X 7 receptor pore. Herein, we have investigated whether the pore activated by the elevation of intracellular Ca 2ϩ concentration is associated to P2X 7 receptor. Using patch clamp in cell attached, whole cell configuration, and dye uptake, we measured the pore opening in cell types that express the P2X 7 receptor (2BH4 cells and peritoneal macrophages) and in cells that do not express this receptor . In 2BH4 cells, the stimulation with ionomycin (5-10 M) increased intracellular free Ca 2ϩ concentration and induced pore formation with conductance of 421 Ϯ 14 pS, half-time (t 1 ⁄2) for ethidium bromide uptake of 118 Ϯ 17 s, and t 1 ⁄2 for Lucifer yellow of 122 Ϯ 11 s. P2X 7 receptor antagonists did not block these effects. Stimulation of HEK-293 and IT45-RI cells resulted in pore formation with properties similar to those found for 2BH4 cells. Connexin hemichannel inhibitors (carbenoxolone and heptanol) also did not inhibit the pore-induced effect following the increase in intracellular Ca 2ϩ concentration. However, 5-(N,N-hexamethylene)-amiloride, a P2X 7 receptor pore blocker, inhibited the induced pore. Moreover, intracellular signaling modulators, such as calmodulin, phospholipase C, mitogen-activated protein kinase, and cytoskeleton components were important for the pore formation. Additionally, we confirmed the results obtained for electrophysiology by using the flow cytometry, and we discarded the possibility of cellular death induced by raising intracellular Ca 2ϩ at the doses used by using lactate dehydrogenase release assay. In conclusion, increased concentration in intracellular Ca ϩ2 induces a novel membrane pore pharmacologically different from the P2X 7 associated pore and hemigap-junction pore.P2X 7 receptor; pore formation; second messenger P2X RECEPTORS are members of a family of P2 receptors with seven subtypes (P2X 1 -P2X 7 ) that induce an increase in intracellular Ca 2ϩ concentration when activated. Among the P2X receptors, P2X 7 subtype is the most divergent component of this family in terms of pharmacological properties, molecular structure, and function (54). This receptor forms a nonselective cation channel upon low ATP concentration, whereas at high ATP concentration, this receptor induces a pore formation that allows the flux of molecules of up to 900 Da and may lead to cell death. Although P2X 7 receptor is associated with expression of both functional channels and large pores, the structure of the large pore-forming subunits and whether the channel and the large pore are the same structure are still not known.From a physiological point of view, P2X 7 is mainly expressed in the immune system found in all cells of this system studied so far. The activation of P2X 7 receptor has several effects in the immune system such as release of mature interleukin-␤ and other pro-inflammatory cytokines (interleukin-18,...

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Section: Phospholipase C Inhibitors Blocked Ionomycin-induced Pore Fomentioning

confidence: 99%

Pharmacological properties of a pore induced by raising intracellular Ca²⁺

Faria¹,

Reis²,

Casabulho³

et al. 2009

American Journal of Physiology-Cell Physiology

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“…Connexins and pannexins have no sequence homology, but they share a common transmembrane topology. They oligomerize around a central pore to form hexameric plasma membrane conduits termed "hemichannels" (for hemi gap junction channels) Barbe et al 2006;Shestopalov and Panchin 2007). Searches of human gene libraries have identified 21 connexins ranging from Cx23 to Cx62 (Söhl and Willecke 2004).…”

mentioning

confidence: 99%

“…Pannexins comprise only three subtypes termed Px1 to Px3 (Litvin et al 2006). Cx43 and Px1 are the most ubiquitous members of each family and they are often endogenously coexpressed in many cell types (Laird et al 2006;Barbe et al 2006;Shestopalov and Panchin 2007;Boassa et al 2007). …”

mentioning

confidence: 99%

Currently Used Methods for Identification and Characterization of Hemichannels

Schalper

Palacios-Prado

Orellana

et al. 2008

Cell Communication & Adhesion

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Connexins and pannexins are vertebrate transmembrane proteins that form hexameric conduits termed hemichannels. Functional hemichannels allow the diffusional transport of ions and small molecules across the plasma membrane and serve as paracrine and autocrine communication pathways. During the last decade, interest in the hemichannel field increased substantially. Today, there is evidence for the existence of connexin hemichannels in vertebrate cells and bulk of information supports their function in diverse physiological and pathological responses. Controversy regarding the molecular identity of the hemichannel type mediating many responses arose recently with the identification of pannexin-based hemichannels. Here, the authors describe the most frequently used methods for studying hemichannels in living mammalian cells and focus on those with which they have more experience. Although the available in vitro evidence is substantial, further studies and possibly new experimental approaches are required to understand the role and properties of connexin and pannexin hemichannels in vivo.

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“…Gap junctions play a role in such communication. Gap junctions are seen in all eumetazoans, with the exception of anthozoans and scyphozoans (Mackie et al, 1984;Shestopalov and Panchin, 2008). Primitive multicellular animals with monociliary cells (sponges and placozoans) do not have gap junctions.…”

mentioning

confidence: 99%