Of the three pannexins in vertebrate proteomes, pannexin1 (Panx1) is the only one well characterized, and it is generally accepted that Panx1 functions as an ATP release channel for signaling to other cells. However, the ATP permeability of the channel is only observed with certain stimuli, including low oxygen, mechanical stress, and elevated extracellular potassium ion concentration. Otherwise, the Panx1 channel is selective for chloride ions and exhibits no ATP permeability when stimulated simply by depolarization to positive potentials. A third, irreversible activation of Panx1 follows cleavage of carboxyterminal amino acids by caspase 3. The selectivity/permeability properties of the caspase cleaved channel are unclear as it reportedly has features of both channel conformations. Here we describe the biophysical properties of the channel formed by the truncation mutant Panx1Δ378, which is identical to the caspase-cleaved protein. Consistent with previous findings for the caspase-activated channel, the Panx1Δ378 channel was constitutively active. However, like the voltage-gated channel, the Panx1Δ378 channel had high chloride selectivity, lacked cation permeability, and did not mediate ATP release unless stimulated by extracellular potassium ions. Thus, the caspase-cleaved Panx1 channel should be impermeable to ATP, contrary to previous claims.
ASJC Scopus subject areas
- Cell Biology