Effects of micromolar and nanomolar calcium concentrations on non-synaptic bursting in the hippocampal slice.

To determine how [Ca2+]0 affects non-synaptic epileptogenesis in the CAI area of hippocampal slices, we compared the extracellularly recorded hyperactivity induced by ACSF containing either micromolar ('low-Ca2+, LC-ACSF) or nanomolar concentrations of Ca2+ ('zero-Ca2+, ZC-ACSF). Both solutions effectively blocked chemical synaptic transmission but spontaneous bursts developed more quickly and consistently in ZC-ACSF and were longer in duration and more frequent than those recorded in LC-ACSF Antidromically evoked bursts were less epileptiform, i.e., they exhibited fewer population spikes (PSs), in ZC-ACSF. Increasing [Mg2+]0 or decreasing [K+]0 suppressed spontaneous LC-ACSF bursting but only decreased the intensity and frequency of bursting in ZC-ACSF. Either manipulation increased the epileptiform nature of the antidromically evoked field potential, thereby mimicking the effect of increasing [Ca2+]0 from nanomolar to micromolar levels. Bath application of 250-500 microM GABA commonly arrested spontaneous bursting in LC-ACSF. In ZC-ACSF, GABA decreased the burst frequency but paradoxically superimposed high amplitude PSs on each burst. These effects were reversed by the GABAA receptor antagonists bicuculline methiodide or picrotoxin (50-100 microM). These results indicate that simply lowering [Ca2+]0 from micromolar to nanomolar concentrations increases the burst propensity and intensity of the CA1 population and can dramatically alter responses to pharmacological agents.