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.