Biphasic effects of gap junctional uncoupling agents on the propagation of retinal spreading depression.

The spreading depression wave of Leão (SD) propagates in the nervous tissue at 3-10 mm/min and is accompanied by an increase of intracellular Ca2+ concentration and a decrease in the extracellular milieu. Recently the spread of Ca2+ waves with propagating velocities of the same order of magnitude has been detected in cultures of nerve cells. It has been suggested that these waves, which can be blocked by gap junctional agents, are related to SD. The present experiments describe some effects of heptanol and octanol (10 microM to 10 mM), well-known uncoupling agents of gap junctions, on the slow voltage changes and the velocity of propagation of Leão's phenomenon in isolated chick retina: 1) a 50 to 700 microM concentration of these alcohols in the superfusate solutions increased the velocity, whereas high concentrations (1 to 10 mM) decreased and subsequently halted the spread; 2) the recovery period of the slow voltage changes of SD was shorter in the presence of alcohol and its amplitude was larger during faster SD waves. These effects were observed in the retina during successive individual waves as well as in the course of circling SD. All of these effects were reversible, without any sign of damage to the retina. In the concentration range of 50 microM to 10 mM, methanol, ethanol, butanol and cyclo-hexanol had no effect on retinal SD. These data suggest the involvement of gap junctions in Leão's wave. This involvement is complex and its functional effects together with other factors that influence the velocity of propagation of SD are being investigated.