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

Threshold determination of spreading depression evoking substances in the retina in vitro

A technique for the determination of the threshold concentrations of chemical substances for elicitation of spreading depression is described. The technique minimizes the interference of mechanical stimulating effects and alterations in the susceptibility of the retina to spreading depression due to changes in unstirred layers at the liquid-tissue interphase. The following threshold concentrations were shown to elicit the wave: 8000-10000 microM KCl, 100-200 microM sodium glutamate, 5-10 microM sodium kainate, 10-20 microM sodium N-methyl-aspartate, 600-1200 microM (NH4)2SO4 and 400-600 microM BaCl2. Variations of K+ or Mg2+ concentration in the standard Ringer solution that may cause an increase or decrease of spreading depression velocity have an inverse effect on the threshold for elicitation of the reaction