Calcium effects on gap junction structure and cell coupling.

Abstract

PROTOPLASMIC molecules of low molecular weight are known to travel freely across the boundaries between most neighbouring cells through small intercellular channels generally thought to be at the intramembranous particles of gap junctions1–3. The permeability of the channels can be decreased to a complete interruption of cell communication by a variety of treatments2–10. Most of these treatments raise the concentration of ionised calcium, [Ca2+], in the cytoplasm8, suggesting that calcium may be the uncoupling agent in both vertebrate9 and invertebrate cells2,8. In some systems glutaraldehyde fixation has also been shown to produce uncoupling3; however, this type of uncoupling does not seem to be triggered by calcium10. In parallel with functional uncoupling reversible structural changes have been described in gap junctions of crayfish characterised by an increase in tightness and regularity of particle aggregation and a decrease in junctional thickness and particle size10. These changes, interpreted as reflecting conformational rearrangements in the protein framework of the channels resulting in channel obliteration, were recently confirmed in the rat11 although in the latter, functional uncoupling was not measured electrophysiologically, but only presumed on the basis of reasonable comparative arguments. It remains uncertain whether or not the changes in both the gap junction structure and the cell coupling are due to a direct action of calcium on the junctional membranes. We show here that the junctional change is indeed a calcium effect, triggered by [Ca2+] as low as 5×10−7 M.