RT Journal Article SR Electronic T1 Pannexin 1: The Molecular Substrate of Astrocyte “Hemichannels” JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7092 OP 7097 DO 10.1523/JNEUROSCI.6062-08.2009 VO 29 IS 21 A1 Rodolfo Iglesias A1 Gerhard Dahl A1 Feng Qiu A1 David C. Spray A1 Eliana Scemes YR 2009 UL http://www.jneurosci.org/content/29/21/7092.abstract AB 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. Here, we provide strong evidence that, in cultured astrocytes, pannexin1 (Panx1) but not Cx43 forms hemichannels. Electrophysiological and fluorescence microscope recordings performed in wild-type and Cx43-null astrocytes did not reveal any differences in hemichannel activity, which was mostly eliminated by treating Cx43-null astrocytes with Panx1-short interfering RNA [Panx1-knockdown (Panx1-KD)]. Moreover, quantification of the amount of ATP released from wild-type, Cx43-null, and Panx1-KD astrocytes indicates that downregulation of Panx1, but not of Cx43, prevented ATP release from these cells.