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Review
. 2014;8(2):103-9.
doi: 10.4161/chan.27545. Epub 2014 Jan 13.

Intrinsic properties and regulation of Pannexin 1 channel

Yu-Hsin Chiu  1 , Kodi S Ravichandran  2 , Douglas A Bayliss  1
Affiliations
Review

Intrinsic properties and regulation of Pannexin 1 channel

Yu-Hsin Chiu et al. Channels (Austin). 2014.

Abstract

Pannexin 1 (Panx1) channels are generally represented as non-selective, large-pore channels that release ATP. Emerging roles have been described for Panx1 in mediating purinergic signaling in the normal nervous, cardiovascular, and immune systems, where they may be activated by mechanical stress, ionotropic and metabotropic receptor signaling, and via proteolytic cleavage of the Panx1 C-terminus. Panx1 channels are widely expressed in various cell types, and it is now thought that targeting these channels therapeutically may be beneficial in a number of pathophysiological contexts, such as asthma, atherosclerosis, hypertension, and ischemic-induced seizures. Even as interest in Panx1 channels is burgeoning, some of their basic properties, mechanisms of modulation, and proposed functions remain controversial, with recent reports challenging some long-held views regarding Panx1 channels. In this brief review, we summarize some well-established features of Panx1 channels; we then address some current confounding issues surrounding Panx1 channels, especially with respect to intrinsic channel properties, in order to raise awareness of these unsettled issues for future research.

Keywords: ATP release; P2X receptor; Pannexin 1; ionic selectivity; unitary conductance.

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Figures

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Figure 1. Channel properties of C-terminally truncated hPanx1. (A) Examples of carbenoxolone-sensitive current obtained from HEK293T cell expressing full-length or C-terminal truncated (ΔC; same as Δ371 in ref. 22) hPanx1 using whole-cell voltage ramp. Note that the full-length hPanx1 does not generate appreciable current. (B) Representative whole-cell recording of hPanx1ΔC with different concentration of HEPES- in the bath. Voltage ramps started with symmetrical Cl- (151 mM), followed by replacing Cl- with HEPES- in the bath while maintaining total anion concentration (Cl- + HEPES- = 161 mM). Note the shift in reversal potential (Erev). Similar results were obtained by measuring tail currents at different repolarization steps following a constant depolarization step (data not shown). (C) Plot of reversal potential obtained in bath solutions containing different HEPES concentrations. Red dots indicated averaged Erev from recordings shown in (B). The dashed lines represent fits to an extended constant field (GHK) equation using relative permeability ratios (PHEPES:PCl of either 0.3 or 0). The data indicate a substantial HEPES permeability in the C-terminally truncated hPanx1 channel. (D) Example of cell-attached recordings of hPanx1ΔC in HEK293T cells at the indicated patch potentials. The patch contained at least 2 active Panx1 channels, as noted by the transitions from the closed state (C) to 1 (O1) and 2 (O2) channel openings of equal amplitude. Carbenoxolone (CBX) inhibited open probability without changing unitary current amplitude, as reported previously. We did not observe multiple subconductance states, even in long duration recordings. (E) Unitary conductance (γ) obtained by analyzing single-channel current amplitude at various patch potentials (from data in [D]).
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