title: The membrane protein Pannexin1 forms two open-channel conformations depending on the mode of activation.
abstract: Pannexin1 (Panx1) participates in several signaling events that involve adenosine triphosphate (ATP) release, including the innate immune response, ciliary beat in airway epithelia, and oxygen supply in the vasculature. The view that Panx1 forms a large ATP release channel has been challenged by the association of a low-conductance, small anion-selective channel with the presence of Panx1. We showed that Panx1 membrane channels can function in two distinct modes with different conductances and permeabilities when heterologously expressed in Xenopus oocytes. When stimulated by potassium ions (K(+)), Panx1 formed a high-conductance channel of ~500 pS that was permeable to ATP. Various physiological stimuli can induce this ATP-permeable conformation of the channel in several cell types. In contrast, the channel had a low conductance (~50 pS) with no detectable ATP permeability when activated by voltage in the absence of K(+). The two channel states were associated with different reactivities of the terminal cysteine of Panx1 to thiol reagents, suggesting different conformations. Single-particle electron microscopic analysis revealed that K(+) stimulated the formation of channels with a larger pore diameter than those formed in the absence of K(+). These data suggest that different stimuli lead to distinct channel structures with distinct biophysical properties.
authors: Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL 33136, USA.
authors: Junjie
authors: J
authors: Wang
authors: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA 92093-06083, USA.
authors: Cinzia
authors: C
authors: Ambrosi
authors: Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL 33136, USA.
authors: Feng
authors: F
authors: Qiu
authors: Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL 33136, USA.
authors: David G
authors: DG
authors: Jackson
authors: National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA 92093-06083, USA. Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-06083, USA.
authors: Gina
authors: G
authors: Sosinsky
authors: Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, FL 33136, USA. gdahl@miami.edu.
authors: Gerhard
authors: G
authors: Dahl
mesh_terms: D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D000255:Adenosine Triphosphate; D011188:Potassium