Cell to cell communication and pH in the frog lens.

Abstract

Fiber cells of the lens are electrically and diffusionally interconnected through extensive gap junctions. These junctions allow fluxes of small solutes to move between inner cells and peripheral cells, where the majority of transmembrane transport takes place. We describe here a method utilizing two intracellular microelectrodes to measure the cell to cell resistance between fiber cells at any given distance into the intact lens. We also use ion-sensitive microelectrodes to record intracellular pH at various depths in the intact lens. We find that gap junctions connecting inner fiber cells differ in pH sensitivity as well as normal coupling resistance from those connecting peripheral cells. The transition occurs in a zone between 500 and 650 microns into the lens. Fiber cells peripheral to this zone have a specific coupling resistance of 1.1 omega cm2, whereas those inside have a specific coupling resistance of 2.7 omega cm2. However, when the cytoplasm of fiber cells is acidified by bubbling with CO2, peripheral cells uncouple and the cell to cell resistance goes up more than 40-fold, whereas junctions inside this zone are essentially unaffected by changes in intracellular pH. In a normal frog lens, the intracellular pH in fiber cells near the lens surface is 7.02, a value significantly alkaline to electrochemical equilibrium. Our data suggest that Na/H exchange and perhaps other Na gradient-dependent mechanisms in the peripheral cells maintain this transmembrane gradient. Deep in the lens, the fiber cell cytoplasm is significantly more acidic (pHi 6.81) due to influx of hydrogen across the inner fiber cell membranes and production of H+ by the inner fiber cells. Because of the normally acid cytoplasm of interior fiber cells, their loss of gap junctional sensitivity to pH may be essential to lens survival.

Functional Role of the Carboxyl Terminal Domain of Human Connexin 50 in Gap Junctional Channels

“…The pH values in the cortex are 7.02-7.2 and 6.3-6.8 in the nucleus (Mathias, Riquelme & Rae, 1991). This pH gradient may result from metabolic accumulation of increasing amounts of lactate as the depth from the cortex increases.…”

Gap Junctions

“…The lens fibers are joined to each other and to the epithelial cells by large numbers of gap junctions (Goodenough 1992). The asymmetric location of the Na þ K þ ATPase in the epithelium results in a translenticular potential and a DC current flow (Candia et al 1970), modeled as the circulatory system of the lens (Rae 1979;Mathias 1985;Mathias and Rae 1989). As the high concentration of the crystallins requires a tight control of ionic balance to remain in solution, the ionic syncytium created by the gap junctions is essential for lens transparency.…”

Oxidative Stress, Lens Gap Junctions, and Cataracts

“…Gap junctions are membrane specializations that contain clusters of intercellular channels that are permeable to ions and molecules up to 1 kDa. Lens fiber cells share ions and small metabolites through gap junction channels, and therefore behave as a functional syncytium (45,91). Epithelial and fiber cells contain morphologically and physiologically distinct gap junctions (95,123).…”