Calmodulin dependent protein kinase increases conductance at gap junctions formed by the neuronal gap junction protein connexin36.

The major neuronal gap junction protein connexin36 (Cx36) exhibits the remarkable property of "run-up", in which junctional conductance typically increases by 10-fold or more within 5-10min following cell break-in with patch pipettes. Such conductance "run-up" is a unique property of Cx36, as it has not been seen in cell pairs expressing other connexins. Because of the recent observation describing CaMKII binding and phosphorylation sites in Cx36 and evidence that calmodulin dependent protein kinase II (CaMKII) may potentiate electrical coupling in neurons of teleosts, we have explored whether CaMKII activates mammalian Cx36.

ATP signaling is deficient in cultured Pannexin1-null mouse astrocytes.

Pannexins (Panx1, 2, and 3) comprise a group of proteins expressed in vertebrates that share weak yet significant sequence homology with the invertebrate gap junction proteins, the innexins. In contrast to the other vertebrate gap junction protein family (connexin), pannexins do not form intercellular channels, but at least Panx1 forms nonjunctional plasma membrane channels. Panx1 is ubiquitously expressed and has been shown to form large conductance (500 pS) channels that are voltage dependent, mechanosensitive, and permeable to relatively large molecules such as ATP.

Pannexin1-mediated ATP release provides signal transmission between Neuro2A cells.

Pannexin1 (Panx1), a protein related to the gap junction proteins of invertebrates, forms nonjunctional channels that open upon depolarization and in response to mechanical stretch and purinergic receptor stimulation. Importantly, ATP can be released through Panx1 channels, providing a possible role for these channels in non-vesicular signal transmission. In this study we expressed exogenous human and mouse Panx1 in the gap junction deficient Neuro2A neuroblastoma cell line and explored the contribution of Panx1 channels to cell-cell communication as sites of ATP release.

Silencing MaxiK activity in corporal smooth muscle cells initiates compensatory mechanisms to maintain calcium homeostasis.

Introduction: The MaxiK potassium channel is regulated by voltage and intracellular calcium, and plays a critical role in regulating intracellular calcium concentration ([Ca(2+) ](i)), which is the ultimate determinant of smooth muscle tone. Tight control of corpus cavernosum smooth muscle (CCSM) tone is critically important and misregulation can result in erectile dysfunction.

Aim: Because of the tight functional linkage of MaxiK and calcium channel activity, the aim of this study was to determine the effects of silencing and pharmacological inhibition of MaxiK on calcium homeostasis and intercellular calcium signaling in CCSM cells.

Mefloquine blockade of Pannexin1 currents: resolution of a conflict.

The authors' laboratory has reported potent block of Pannexin1 (Panx1) currents by the antimalarial quinine derivative mefloquine. However, other laboratories have found little or no mefloquine sensitivity of Panx1 currents or processes attributable to these channels. In order to resolve this issue, the authors have performed extensive dose-response studies on Panx1-transfected neuroblastoma (Neuro2A) and rat insulinoma (Rin) cells, comparing mefloquine obtained from three suppliers and also comparing the sensitivity to diastereomers.

Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes.

Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels.

Pannexin 1: the molecular substrate of astrocyte "hemichannels".

Purinergic signaling plays distinct and important roles in the CNS, including the transmission of calcium signals between astrocytes. Gap junction hemichannels are among the mechanisms proposed by which astrocytes might release ATP; however, whether the gap junction protein connexin43 (Cx43) forms these "hemichannels" remains controversial. Recently, a new group of proteins, the pannexins, have been shown to form nonselective, high-conductance plasmalemmal channels permeable to ATP, thereby offering an alternative for the hemichannel protein.