Lens Connexin Channels Have Differential Permeability to the Second Messenger cAMP

Area of Science:

• Cell Biology
• Biophysics
• Ophthalmology

Background:

• Gap junction channels, formed by connexins, mediate intercellular communication.
• Connexins have specific biophysical properties affecting solute passage, including second messengers.
• Lens connexins are crucial for epithelial cell division and differentiation.

Purpose of the Study:

• To investigate the cyclic adenosine monophosphate (cAMP) permeability of lens connexins (Cx43, Cx46, Cx50).
• To understand how cAMP passage through these channels influences lens cell functions.

Main Methods:

• Simultaneous measurement of junctional conductance and intercellular cAMP transfer.
• Utilized a cAMP sensor (SpIH) in recipient cells for detection.
• Introduced cAMP via patch pipette and recorded SpIH-derived currents.
• Direct visualization of cAMP permeability using fluorescently tagged cAMP.

Main Results:

• Homotypic Cx43 channels showed significant cAMP transfer.
• Homotypic Cx46 channels exhibited cAMP transfer, but with reduced permeability compared to Cx43.
• Homotypic Cx50 channels displayed extremely low permeability to cAMP.

Conclusions:

• Cx43 and Cx46 channels facilitate intercellular cAMP delivery, sufficient to activate cyclic nucleotide-modulated channels.
• The low cAMP permeability of Cx50 channels may regulate cell division in the lens.