Biomedical subjects

Silviu Locovei

Publications and source records attributed to Silviu Locovei.

4 recordsLinked to original sources

PubMed2006

Pannexin 1 in erythrocytes: function without a gap.

ATP is a widely used extracellular signaling molecule. The mechanism of ATP release from cells is presently unresolved and may be either vesicular or channel-mediated. Erythrocytes release ATP in response to low oxygen or to shear stress. In the absence of vesicles, the release has to be through channels. Erythrocytes do not form gap junctions. Yet, here we show with immunohistochemical and electrophysiological data that erythrocytes express the gap junction protein pannexin 1. This protein, in addition to forming gap junction channels in paired oocytes, can also form a mechanosensitive and ATP-permeable channel in the nonjunctional plasma membrane. Consistent with a role of pannexin 1 as an ATP release channel, ATP release by erythrocytes was attenuated by the gap junction blocker carbenoxolone. Furthermore, under conditions of ATP release, erythrocytes took up fluorescent tracer molecules permeant to gap junction channels.

Adenosine Triphosphate↗

PubMed2006

Pannexin: to gap or not to gap, is that a question?

Vertebrates express two families of gap junction proteins: the well characterized connexins and the recently discovered pannexins. The latter are related to invertebrate innexins. Here we present the hypothesis that pannexins, rather than providing a redundant system to gap junctions formed by connexins, exert a physiological role as nonjunctional membrane channels. Specifically, we propose that pannexins can serve as ATP release channels. This function presumptively is also performed by innexins in invertebrates, in addition to their traditional gap junction role.

Animals↗

PubMed2005

Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium.

The ability for long-range communication through intercellular calcium waves is inherent to cells of many tissues. A dual propagation mode for these waves includes passage of IP3 through gap junctions as well as an extracellular pathway involving ATP. The wave can be regenerative and include ATP-induced ATP release via an unknown mechanism. Here, we show that pannexin 1 channels can be activated by extracellular ATP acting through purinergic receptors of the P2Y group as well as by cytoplasmic calcium. Based on its properties, including ATP permeability, pannexin 1 may be involved in both initiation and propagation of calcium waves.

Adenosine Triphosphate↗

PubMed2004

Pannexin membrane channels are mechanosensitive conduits for ATP.

Intercellular calcium wave propagation initiated by mechanical stress is a phenomenon found in nearly all cell types. The waves utilize two pathways: transfer of InsP3 directly from cell to cell through gap junction channels and release of ATP onto extracellular purinergic receptors. The conduit for ATP has remained elusive and both a vesicular and a channel mediated release have been considered. Here, we describe the properties of single pannexin 1 channels. They have a wide expression spectrum, they are of large conductance and permeant for ATP, and they are mechanosensitive. Hence, pannexins are candidates for the release of ATP to the extracellular space upon mechanical stress.

Animals↗