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Selectivity of connexin-specific gap junctions does not correlate with channel conductance
R D Veenstra1, H Z Wang, D A Beblo
1Department of Pharmacology, State University of New York Health Science Center at Syracuse 13210, USA.
Circulation Research
|December 1, 1995
Summary
Connexin channels exhibit diverse permeabilities and selectivities, challenging the traditional pore size model. New research suggests electrostatic interactions govern connexin channel function, independent of conductance.
Area of Science:
- Cellular Biology
- Biophysics
- Molecular Biology
Background:
- Connexins form gap junction channels with varying expression and conductance (gamma j).
- The relationship between connexin channel conductance and specific ionic/molecular permeabilities remains unclear.
- Conventional models link conductance to pore diameter, predicting permeability changes with size.
Purpose of the Study:
- To investigate if connexin-specific channels have distinct ionic and molecular permeabilities.
- To test the conventional model's assumption that conductance is determined by pore diameter.
- To explore alternative mechanisms for connexin channel selectivity and conductance.
Main Methods:
- Functional expression of rat, chicken, and human connexin channels in N2A cells.
- Ion substitution techniques (KCl for potassium glutamate) to determine unitary conductance ratios.
- Dye transfer assays using fluorescein derivatives to assess molecular size permeability.
- Comparison of experimental data with predictions from the Goldman-Hodgkin-Katz equation.
Main Results:
- All five connexin channels tested displayed a range of selectivities and permeabilities.
- These properties were independent of the channel's unitary conductance (gamma j).
- Results contradicted the conventional model linking conductance solely to pore diameter.
Conclusions:
- The conventional aqueous pore model is insufficient to explain connexin channel function.
- Electrostatic interactions likely play a crucial role in determining connexin channel conductance and permselectivity.
- Connexin channels may share selectivity mechanisms with other ion channel classes, such as Na+ and K+ channels.