Permeability of cell junction depends on local cytoplasmic calcium activity

Abstract

MANY kinds of cells are coupled by junctions consisting of membrane channels through which molecules of a certain size range can flow freely from one cell interior to another¹. It has been proposed that the permeability of the junctional channels depends on the concentration of free ionised calcium in cytoplasm ([Ca²⁺]_i) (ref. 2). This hypothesis is supported by two classes of experiments. In one, the interior of a coupled cell system is allowed ito exchange freely with a known [Ca²⁺] in the exterior, through a hole in the (non-junctional) membrane; junctional conductance is reduced (uncoupling) when the [Ca²⁺]_i is above 5–8 × 10⁻⁵ M (ref. 3). In the other class, uncoupling ensues when the (closed) cell system is treated with inhibitors of energy metabolism or with Ca²⁺ ionophores⁵, or on exposure for long periods to Ca,Mg-free medium or to Li medium⁶; in these conditions a rise in [Ca²⁺]_i, may be expected because of known properties of cellular Ca metabolism^7,8. Here, we demonstrate the changes in [Ca²⁺]_i together with those in coupling in three of these conditions, using aequorin to display the distribution of Ca²⁺ in the cell. It will be shown that the uncoupling is, indeed, in each case associated with a rise in [Ca²⁺]. Furthermore, by local injection of Ca²⁺ into the cells, it will be shown that uncoupling ensues when the rise in [Ca²⁺]_i occurs at the junction, but not when it occurs at other regions in the cell.