Epileptiform activity induces distance-dependent alterations of the Ca2+ extrusion mechanism in the apical dendrites of subicular pyramidal neurons

The cellular and molecular mechanisms that underlie acquired changes in Ca2+ dynamics of different neuronal compartments are important in the induction and maintenance of epileptiform activity. Simultaneous electrophysiology and Ca2+ imaging techniques were used to understand the basic properties of dendritic Ca2+ signaling in rat subicular pyramidal neurons during epileptiform activity. Distance-dependent changes in the Ca2+ decay kinetics locked to spontaneous epileptiform discharges and back-propagating action potentials were observed in the apical dendrites. A decrement in the mean tau value of Ca2+ decay was observed in distal parts (95-110 mu m) of the apical dendrites compared with proximal segments (30-45 mu m) in in-vitro epileptic conditions but not in control. Pharmacological agents that block Ca2+ transporters, i.e. Na+/ Ca2+ exchangers (Benzamil), plasma membrane Ca2+-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca2+-ATPase pumps (Thapsigargin), were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca2+ extrusion mechanisms. The relative contribution of Na+/Ca2+ exchangers in Ca2+ extrusion was higher in the distal apical dendrites in the in-vitro epileptic condition and this property modulated the excitability of the neuron in simulation. The Ca2+ homeostatic mechanisms that restore normal Ca2+ levels could play a major neuroprotective role in the distal dendrites that receive synaptic inputs.