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Connexin Specificity of Second Messenger Permeation: Real Numbers At Last

The Journal of General Physiology
The Rockefeller University Press
Publication Date
DOI: 10.1085/jgp.200809998
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untitled Th e Jo ur na l o f G en er al P hy si o lo g y J. Gen. Physiol. © The Rockefeller University Press $30.00 Volume 131 Number 4 April 2008 287–292 287 C O M M E N TA RY Correspondence to a h a r r i s @ u m d n j . e d u The discovery many years ago that ions and cytoplasmic molecules could diffuse between cells via gap junction channels inspired excited speculation about the roles such intercellular communication could play in develop- ment, physiology, and pathology. This view was rein- forced when it later emerged that there are many types of gap junction channels, with � 20 functionally distinct vertebrate isoforms of the component protein (con- nexin), which can combine in homomeric and hetero- meric channel structures that have distinct conductance, dye permeability, and gating properties. The unitary conductances range from 10 pS to 300 pS; their cation/ anion permeability ratios ( P K+ / P Cl – ) range from � 8.0 to � 0.8 and their permeabilities to fl uorescent tracers are highly disparate. None of these parameters correlate with each other ( Harris, 2001 ). What is all this variability good for? It seems unlikely to be all about electrical coupling; it makes more sense to think that the distinct pore/permeability properties are important and perhaps designed for the ability to defi ne, mediate, and dynamically modulate the vocabu- lary of intercellular molecular signals. In fact, evidence for the importance of gap junction as conduits of intercellular molecular signals is growing. In recent years it has been demonstrated, in mostly qualitative ways, that different types of connexin chan- nels have different effective permeabilities to specifi c cytoplasmic molecules, and that the permeability differ- ences among connexin channels cannot be readily in- ferred from other known functional features. This work has increased speculation that (a) the pores of connexin

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