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Gap junction channels: distinct voltage-sensitive and -insensitive conductance states
A P Moreno1, M B Rook, G I Fishman
1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.
Biophysical Journal
|July 1, 1994
Summary
Connexin43 gap junction channels exhibit a persistent, voltage-insensitive conductance (gmin) even at high transjunctional voltages. This residual conductance arises from a specific substate within connexin43 channels, not separate channels.
Area of Science:
- Cellular biology
- Biophysics
- Neuroscience
Background:
- Mammalian gap junction channels, including connexin43 (Cx43), are voltage-sensitive.
- Transjunctional voltages (Vj) above +/- 50 mV typically reduce junctional conductance (gj) for Cx43.
- A residual voltage-insensitive conductance (gmin) persists even at high Vj.
Purpose of the Study:
- To investigate the mechanism underlying the voltage-insensitive component (gmin) of connexin43 (Cx43) gap junction conductance.
- To determine if gmin arises from separate channels or a substate of Cx43 channels.
Main Methods:
- Utilized cell types with endogenous Cx43 and hepatoma cells transfected with Cx43 cDNA.
- Performed voltage clamp studies to measure maximal junctional conductance (gmax) and residual conductance (gmin).
- Conducted single-channel analyses to differentiate conductance components.
Main Results:
- The ratio of gmin/gmax remained constant (0.4-0.5) across varying gmax values.
- Single-channel studies indicated different channel sizes for voltage-sensitive and -insensitive components.
- Cx43 channel open times decreased at high voltages, yet gmin persisted.
Conclusions:
- The voltage-insensitive conductance (gmin) is attributable to a voltage-insensitive substate of connexin43 channels.
- This suggests that connexin43 channel closure in response to stimuli can be graded, not all-or-none.