Spreading depression (SD) is a propagating wave of neuronal activity in the central nervous system and may play a role in triggering classical migraine. The retina serves as a model system for examining the phenomenon of SD and the influence of various drugs on it. After a SD wave passes a new wave can not be elicited in the absolute refractory period of the tissue (about 2 min), this is followed by a relative refractory phase of about 20 min before complete recovery. The aim of the present study was to describe the effects of Ba2+, a blocker of glial cell 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 mechanisms underlying this modulation. Two properties of SD, which are highly sensitive to any changes in the experimental conditions, are the propagation velocity of the wave and the accompanying slow negative potential shift. We measured the propagation velocity and the field potential amplitude in the chicken retina as a function of the recovery state of the tissue under control conditions and compared them with measurements in the presence of Ba2+, octanol or diethylbarbiturate. Under these conditions the manner of the recovery of the tissue changed significantly. Although after blocking the glial (Müller) cell K+ channels with Ba2+ (200 microM), 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 in the recovered retina to 84% of the control velocity. The importance of electrical coupling in the refractory phase and in the recovered tissue was examined by adding octanol (1 mM) to the perfusion solution. In this case the relative recovery phase was shortened and the field potential amplitude (110% of control) and propagation velocity (112% of control) are increased in the completely recovered retina. With the GABA(A)-chloride channel-activating drug diethylbarbiturate (800 microM) the propagation velocity (112% of control) and the amplitude of the field potential (111% of control) in the complete recovered retina are increased, but this seems to have no influence on the refractory state.
We used anemone toxin II (ATX II) to study how a selective enhancement of persistent Na+ current (INaP) would affect the excitability of CA1 pyramidal neurons in the hippocampal slice. In whole-cell recordings from CA1 cell somata, local application of ATX II (10 microM) into the stratum pyramidale invariably depolarized the neurons and produced sustained burst discharges with depolarizing plateau potentials of variable amplitude and length. However, the strong excitatory action of ATX II, observed on the single cell level, was not mirrored in field potential recordings from the same hippocampal subfield. The amplitude of the electrically evoked population spike declined, reflecting the decreased availability of fast Na+ channels, and the intracellulary recorded burst discharges were not detected by the field electrode. The lacking synchronization of cellular bursting activity was seen during both local and bath application of ATX II, suggesting that the toxin, in addition to promoting burst discharges of individual neurons, simultaneously dampens network excitability. In fact, ATX II reduced afferent fibre volleys (reflecting axonal excitability) and field excitatory postsynaptic potentials (EPSPs) in a similar fashion. As the expression of different Na+ channel subtypes appears to be compartmentalized within hippocampal neurons, we propose that point mutations leading to pathologically enhanced INaP might exert quite opposite effects, depending on the type and location of the Na+ channel affected. Whereas alterations of somatodendritic Na+ channels would give rise to bursting activity, alterations of axonal Na+ channels would primarily decrease network excitability.
To describe the spatio-temporal patterns of excitable media, the relationship between frequency and propagating velocity of a wave (dispersion relation) is an important issue. Spreading depression (SD) waves in the brain and especially in the retina are an example of self-organized waves in excitable media (here in neuronal tissue). In the retina such waves are accompanied by a remarkable intrinsic optic signal (IOS), which allows to study the wave by standard video imaging techniques. In this study the dispersion relation of SD waves was investigated under different conditions. As expected from standard theories of excitable media, the velocity is a monotone function of the repetition rate, i.e. of the recovery state, with an absolute refractory phase of about 2.4 min. By increasing the temperature, the shape of the curve changes in a significant way. Physiological and theoretical considerations are given for the variation of the dispersion relation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.