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

The spreading depression wave of Leäo (SD) propagates in the nervous tissue at 3-10 mm/min and is a 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 (10µM to 10mM), well-known uncoupling agents of gap junctions, on the slow voltage changes and the velocity of propagation of Leäo's phenomenon in isolated chick retina: 1) a 50 to 700 µM concentration of these alcohols in the superfusate solutions increased the velocity, whereas high concentration (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 µM, methanol, ethanol, butanol and cyclo-hexanol had no effect on retinal SD. These data suggest the involvement of gap junctions in Leäo's wave. This involvement is complex and its functional effects together with other factors that influence the velocity of propagation of SD sre being investigated

Elicitation of retinal spreading depression by barium ions

The association of potassium ions with the occurrence and propagation of spreading depression is well known. The effects of barium ions, a potassium-channel blocker, on spreading depression in isolated retina are described. Pulses of 1-4 mM BaCl2, when applied to the retina, first induce the reaction, the hinder the propagation of the wave which finally stops. The threshold level wihich triggers the reaction is 0.4-0.6 mM BaCl2 but it varies with the composition of the superfusing Ringer solution. For example, in retinas superfused with low NaCl, or NaCl partially substituted by sodium isothionate, spreading depression may be evoked by barium ions at micromolar concentrations, without changing the velocity of spreading. The delayed blocking actions observed with higher doses may predominantly affect the recovery processes of the wave front, and are related to the refractory period of a preceding spreading depression

Spreading depression: a neurohumoral reaction

1. The main characteristics of spreading depression are a decrease of spontaneous electrical activity, slow negative potential changes, transmembrane ion translocations, and an increase in tissue lactate. This is a general phenomenon in the central nervous system. 2. Retinal spreading depression, a very useful model for this phenomenon, has been extensively studied in terms of its optical, electrical and mechanical components. Ionic changes in the extracellular microenvironment have also been assessed and chemical substances liberated from tissue have been detected. 3. The velocity of propagation has been measured and some physical and chemical factors underlying the spread of the electrophysiological depression have been identified. Hypotheses about the nature of the reaction are discussed.