Disruption of Salt Bridge Interactions Modifies Gating Kinetics of Connexin Hemichannels

Gating and regulation of connexin 43 (Cx43) hemichannels.

Connexin 43 (Cx43) nonjunctional or "unapposed" hemichannels can open under physiological or pathological conditions. We characterize hemichannels comprised of Cx43 or Cx43-EGFP (Cx43 with enhanced GFP fused to the C terminus) expressed in HeLa cells. Channel opening was induced at potentials greater than +60 mV. Open probability appeared to be very low. No comparable opening was detected in th...

Connexin hemichannels in the lens

The normal function and survival of cells in the avascular lens is facilitated by intercellular communication through an extensive network of gap junctions formed predominantly by three connexins (Cx43, Cx46, and Cx50). In expression systems, these connexins can all induce hemichannel currents, but other lens proteins (e.g., pannexin1) can also induce similar currents. Hemichannel currents have...

Regulation of Connexin Hemichannels by Monovalent Cations

Opening of connexin hemichannels in the plasma membrane is highly regulated. Generally, depolarization and reduced extracellular Ca2+ promote hemichannel opening. Here we show that hemichannels formed of Cx50, a principal lens connexin, exhibit a novel form of regulation characterized by extraordinary sensitivity to extracellular monovalent cations. Replacement of extracellular Na+ with K+, whi...

Role of Connexin Hemichannels in Neurodegeneration

Divalent Cations Regulate Connexin Hemichannels by Modulating Intrinsic Voltage-dependent Gating

Connexin hemichannels are robustly regulated by voltage and divalent cations. The basis of voltage-dependent gating, however, has been questioned with reports that it is not intrinsic to hemichannels, but rather is derived from divalent cations acting as gating particles that block the pore in a voltage-dependent manner. Previously, we showed that connexin hemichannels possess two types of volt...