Abstract
Pannexin1 (Panx1) participates in several signaling events that involve
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.
