PHARMACOLOGICAL MODULATION OF THE REFRACTORY PERIOD OF RETINAL SPREADING DEPRESSION

Spreading depression (SD) is a propagating wave of neuronal activity i n the central nervous system and may play a role in triggering classic al migraine. The retina serves as a model system for examining the phe nomenon of SD and the influence of various drugs on it. After a SD wav e passes a new wave can not be elicited in the absolute refractory per iod of the tissue (about 2 min), this is followed by a relative refrac tory phase of about 20 min before complete recovery. The aim of the pr esent study was to describe the effects of Ba2+, a blocker of glial ce ll K+ channels, octanol, a gap junction blocker and diethylbarbiturate , a GABA(A) chloride channel-activating drug on the modulation of the refractory period of the retinal SD and to examine the possible mechan isms underlying this modulation. Two properties of SD, which are highl y sensitive to any changes in the experimental conditions, are the pro pagation velocity of the wave and the accompanying slow negative poten tial shift. We measured the propagation velocity and the field potenti al amplitude in the chicken retina as a function of the recovery state of the tissue under control conditions and compared them with measure ments in the presence of Ba2+, octanol or diethylbarbiturate. Under th ese conditions the manner of the recovery of the tissue changed signif icantly. Although after blocking the glial (Muller) cell K+ channels w ith Ba2+ (200 mu M), the curve of recovery of the propagation velocity to its maximum value has the same shape as under control conditions, the propagation velocity is reduced in the whole recovery period and i n the recovered retina to 84% of the control velocity. The importance of electrical coupling in the refractory phase and in the recovered ti ssue was examined by adding octanol (1 mM) to the perfusion solution. in this case the relative recovery phase was shortened and the field p otential amplitude (110% of control) and propagation velocity (112% of control) are increased in the completely recovered retina. With the G ABA(A)-chloride channel-activating drug diethylbarbiturate (800 mu M) the Propagation velocity (112% of control) and the amplitude of the fi eld potential (111% of control) in the complete recovered retina are i ncreased, but this seems to have no influence on the refractory state.