Physiological Modulation of Gap Junction Permeability

Abstract

In many tissues cells communicate directly through arrays of intercellular channels which are organized to form gap junctions. These channels are permeant to inorganic ions as well as to small hydrophilic molecules up to Mr2000. The electrical and chemical coupling provided by such junctions is under the control of intracellular and, in many cases, extracellular substances. The latter (hormones or neurotransmitters) function via the activation of intracellular second messengers. These can rapidly affect the state of opening of the junctions, or induce long-term modulation of the coupling. What are the second messengers and how do they control the functional state of the junctions? These questions remain largely unanswered, although several internal molecules are thought to be involved in these modulations (e.g. Ca2+, H+ or cyclic AMP). The double patch-clamp technique which enables control of both the intracellular milieu and high resolution measurement of transjunctional currents, has recently been applied to study these problems. In particular, it is now possible to examine at the single channel level how junctional conductance is modulated in terms, for example, of the number of open channels or channel elementary properties.